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中华麻醉学杂志
中华麻醉学杂志

罗爱伦

月刊

0254-1416

cja@vip.163.com

0311-85989621

050071

石家庄市和平西路299号

中华麻醉学杂志/Journal Chinese Journal of AnesthesiologyCSCD北大核心CSTPCD
查看更多>>1981年3月创刊，中华医学会主办。本刊是反映了我国麻醉学临床、科研发展的水平，促进了国内外麻醉学科的学术交流，引导着我国麻醉学的发展方向；杂志发行世界104个国家，编委会中有美国、加拿大、新加坡、台湾地区、香港地区的国际知名专家加盟，被《化学文摘》等国际检索系统收录，且荣登《化学文摘》千刊表；首批获准加入WHO西太平洋地区医学索引。曾荣获 “百种中国杰出学术期刊”及“中国精品科技期刊”称号。
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    咪达唑仑口服溶液用于门诊患儿全麻下根管治疗术前镇静的效果

    杨智虎邢飞程丹渠明翠...
    53-57页
    查看更多>>摘要：目的 评价咪达唑仑口服溶液用于门诊患儿全麻下根管治疗术前镇静的效果。 方法 拟行门诊全麻下根管治疗的患儿147例，性别不限，年龄2～7岁，体质量10～30 kg，ASA分级Ⅰ或Ⅱ级，采用随机数字表法分为3组(n＝49)：咪达唑仑口服溶液组(OM组)、咪达唑仑注射液组(M组)和右美托咪定组(D组)。OM组口服咪达唑仑口服溶液0.5 mg/kg＋安慰剂(按照体重计算的等量生理盐水)滴鼻，M组口服咪达唑仑注射液0.5 mg/kg＋安慰剂滴鼻，D组口服安慰剂＋右美托咪定2 μg/kg滴鼻。记录入室后诱导期依从性量表(ICC)评分、镇静良好(ICC评分≤3分)情况、药物接受度评分、面罩接受度评分和分离焦虑评分。记录苏醒时间、PACU停留时间和术中、PACU期间心动过缓、低血压、低氧血症、喉痉挛等发生情况。 结果 最终纳入143例患儿，OM组和M组各48例，D组47例。与M组和D组相比，OM组入室时ICC评分降低，镇静良好率升高，药物接受度评分升高，分离焦虑评分降低，面罩接受度评分降低(P<0.05)；与D组相比，M组入室时ICC评分降低，镇静良好率升高，面罩接受度评分降低(P<0.05)。3组苏醒时间、PACU停留时间、术中和PACU期间不良反应发生率比较差异无统计学意义(P>0.05)。 结论 咪达唑仑口服溶液用于门诊患儿全麻下根管治疗术前镇静的效果好，不良反应少。 Objective To evaluate the efficacy of oral midazolam solution for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia. Methods One hundred and forty-seven pediatric patients of either sex, aged 2-7 yr, weighing 10-30 kg, of American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ, were divided into 3 groups (n=49 each) using a random number table method: oral midazolam solution group (OM group), midazolam injection group (M group), and dexmedetomidine group (D group). In OM group, patients received oral midazolam solution at a dose of 0.5 mg/kg along with a placebo (an equivalent amount of normal saline based on body weight) administered via nasal drops. In M group, patients were given oral midazolam injection at a dose of 0.5 mg/kg along with a placebo via nasal drops. In D group, patients were administered a placebo orally along with dexmedetomidine at a dose of 2 μg/kg via nasal drops. The Induction Compliance Checklist (ICC) scores upon entering the operating room, sedation success rates (ICC score ≤ 3), drug acceptance scores, mask acceptance scores, and separation anxiety scores were recorded. The emergence time, time of stay in postanesthesia care unit (PACU), and occurrence of adverse events such as bradycardia, hypotension, hypoxemia, and laryngospasm during surgery and in PACU were recorded. Results A total of 143 pediatric patients were finally included in the study, with 48 cases in OM group, 48 cases in M group and 47 cases in D group. Compared with M and D groups, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, drug acceptance scores were increased, separation anxiety scores were decreased, and mask acceptance scores were decreased in OM group (P<0.05). Compared with D group, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, and mask acceptance scores were decreased in M group (P<0.05). There were no statistically significant differences in the emergence time, time of stay in PACU, and incidence of adverse events during surgery and in PACU among the three groups (P>0.05). Conclusions Oral midazolam solution provides good effect with less adverse reactions when used for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia.

    咪达唑仑口服液儿童根管疗法清醒镇静

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    艾司氯胺酮复合丙泊酚用于孤独症患儿内镜肠道植管术麻醉的效果

    缪燕香郑明辉冯金香李青...
    58-62页
    查看更多>>摘要：目的 评价艾司氯胺酮复合丙泊酚用于孤独症患儿内镜肠道植管术(TET)麻醉的效果。 方法 选择2022年10月至2023年8月行结肠途径TET的孤独症患儿60例，性别不限，年龄3～12岁，体质量15～45 kg，ASA分级Ⅰ或Ⅱ级，采用随机数字表法分为2组(n＝30)：生理盐水＋丙泊酚组(NP组)和艾司氯胺酮＋丙泊酚组(EP组)。NP组静脉注射生理盐水10 ml，EP组静脉注射艾司氯胺酮0.3 mg/kg，均于30 s后静脉注射丙泊酚2.0 mg/kg。改良警觉/镇静(MOAA/S)评分≤2分时行TET，若镇静深度不够则追加丙泊酚0.5～1.0 mg/kg，维持MOAA/S评分≤2分至术毕。记录患儿TET过程中的体动反应程度。记录注射痛、丙泊酚总用量、手术时间、自然苏醒时间、手术完成情况；记录术中及苏醒期呼吸抑制、恶心呕吐、低血压、心动过缓、术后躁动等不良反应发生情况。 结果 与NP组比较，EP组术中体动程度更轻，丙泊酚总用量、注射痛及术中低血压的发生率降低(P<0.05)，自然苏醒时间及恢复期间不良反应发生率差异无统计学意义(P>0.05)。 结论 艾司氯胺酮(0.3 mg/kg)复合丙泊酚(2.0 mg/kg)可安全、有效地用于孤独症患儿TET，在不进行早期唤醒的复苏策略中，艾司氯胺酮并未增加复苏期间不良反应发生风险。 Objective To evaluate the efficacy of esketamine combined with propofol for colonic transendoscopic enteral tubing (TET) in pediatric patients with autism. Methods Sixty pediatric patients with autism of both sexes, aged 3-12 yr, weighing 15-45 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who underwent painless transendoscopic enteral tubing (TET) from October 2022 to August 2023, were selected and divided into 2 groups (n=30 each) by a random number table method: normal saline + propofol group (group NP) and esketamine + propofol group (group EP). In group NP, normal saline 10 ml was intravenously injected, and 30 s later propofol 2.0 mg/kg was given. In group EP, esketamine 0.3 mg/kg (diluted to 10 ml in normal saline) was intravenously injected, and 30 s later propofol 2.0 mg/kg was given. TET was performed when the Modified Observer′s Assessment of Alertness/Sedation Scale score ≤2. Propofol 0.5-1.0 mg/kg was added if the sedation depth was not enough, and the Modified Observer′s Assessment of Alertness/Sedation Scale score was maintained ≤2 until the end of surgery. The degree of body movement during TET was observed and recorded. The injection pain during induction, total consumption of propofol, operation time, spontaneous emergence time, and completion of operation were recorded. Adverse reactions such as respiratory depression, nausea and vomiting, hypotension, bradycardia, and postoperative agitation were recorded during operation and in the emergence period. Results Compared with group NP, the degree of intraoperative body movement was significantly lighter, the total consumption of propofol and incidence of injection pain and intraoperative hypotension were significantly lower, and no significant change was found in the spontaneous emergence time and incidence of adverse reactions during recovery in group EP (P<0.05). Conclusions Esketamine (0.3 mg/kg) combined with propofol (2.0 mg/kg) can be safely and effectively used for colonic TET in pediatric patients with autism, and esketamine does not increase the risk of adverse reactions during resuscitation in a resuscitation strategy without early awakening.

    氯胺酮二异丙酚孤独性障碍儿童结肠镜检查粪菌移植经内镜肠道植管术

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    复合舒芬太尼时甲苯磺酸瑞马唑仑用于儿童意识消失的药效学

    王少超王磊王超赵文...
    63-65页
    查看更多>>摘要：目的 评价复合舒芬太尼时甲苯磺酸瑞马唑仑用于儿童意识消失的药效学。 方法 拟行电子支气管镜检查术患儿，性别不限，年龄3～6岁，ASA分级Ⅰ或Ⅱ级。所有患儿入室后心电监护，缓慢静脉注射舒芬太尼0.1 μg/kg，3 min后静脉注射甲苯磺酸瑞马唑仑。采用Dixon改良序贯法进行试验，甲苯磺酸瑞马唑仑初始剂量为0.30 mg/kg，根据意识是否消失确定下一例患儿甲苯磺酸瑞马唑仑的剂量，相邻剂量梯度为0.05 mg/kg，意识消失标准：甲苯磺酸瑞马唑仑注射完毕1 min后睫毛反射消失且改良警觉/镇静评分达到0分，直至出现8个意识未消失-意识消失的交叉点。采用probit法计算甲苯磺酸瑞马唑仑使儿童意识消失的半数有效剂量(ED50)、95%有效剂量(ED95)及其95%可信区间(95%CI)。 结果 复合舒芬太尼时甲苯磺酸瑞马唑仑使儿童意识消失的ED50及其95%CI为0.461(0.429～0.493) mg/kg，ED95及其95%CI为0.515(0.487～0.689) mg/kg。 结论 复合舒芬太尼时甲苯磺酸瑞马唑仑使儿童意识消失的ED50为0.461 mg/kg，ED95为0.515 mg/kg。 Objective To evaluate the pharmacodynamics of remimazolam tosilate inducing loss of consciousness (LOC) when combined with sufentanil in children. Methods American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ pediatric patients of either sex, aged 3-6 yr, undergoing electronic bronchoscopy, were included in this study. ECG monitoring was carried out in all children after admission, sufentanil 0.1 μg/kg was intravenously injected slowly, and 3 min later remidazolam tosilate was intravenously injected. The dose of remimazolam tosilate was determined by the modified Dixon′s up-and-down sequential experiment, and the initial dose of remimazolam tosilate was 0.30 mg/kg. The dose of remimazolam tosilate in the next child was determined according to the the loss of consciousness, and the successive dose gradient was 0.05 mg/kg. Loss of eyelash reflex and Modified Observer′s Assessment of Alertness/Sedation Scale score reaching 0 and the occurrence of 8 crossover points where consciousness transitioned from non-disappearance to disappearance after 1 min of remimazolam tosilate injection were considered to be signs of LOC. The median effective dose (ED 50), 95% effective dose (ED95), and their 95% confidence interval (CI) of remimazolam tosilate inducing LOC were calculated using probit method. Results When combined with sufentanil, the ED50 and 95% CI of remimazolam tosilate inducing loss of consciousness were 0.461 (0.429-0.493) mg/kg, and the ED95 and 95% CI were 0.515 (0.487-0.689) mg/kg. Conclusions When combined with sufentanil, the ED50 of remimazolam tosilate inducing LOC is 0.461 mg/kg and the ED95 is 0.515 mg/kg in children.

    舒芬太尼儿童剂量效应关系,药物

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    nNOS-NOS1AP复合体在瑞芬太尼诱发大鼠痛觉过敏中的作用

    舒瑞辰李媛张璇张增利...
    66-70页
    查看更多>>摘要：目的 评价神经元型一氧化氮合酶(nNOS)-一氧化氮合酶1衔接蛋白(NOS1AP)复合体在瑞芬太尼诱发大鼠痛觉过敏中的作用。 方法 清洁级健康成年雄性SD大鼠40只，体质量240～260 g，2～3月龄，采用随机数字表法分为4组(n＝10)：对照组(C组)静脉输注生理盐水0.1 ml·kg－1·min－1 60 min；瑞芬太尼组(R组)静脉输注瑞芬太尼1.0 μg·kg－1·min－1 60 min；nNOS-NOS1AP抑制剂ZLc002组(C＋Z组)和瑞芬太尼＋ZLc002组(R＋Z组)每天腹腔注射ZLc002 10 mg/kg，连续3 d，然后分别静脉输注生理盐水0.1 ml·kg－1·min－1或瑞芬太尼1.0 μg·kg－1·min－160 min。分别于静脉输注前24 h和输注结束后6、24、48 h(T0-3)时测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL)。最后一次痛阈测定结束后处死大鼠，取L4-6脊髓组织，采用RT-PCR法检测脊髓nNOS、NOS1AP、G蛋白信号传导激活蛋白1(Dexras1)的mRNA表达；生物素转化法提取亚硝基化蛋白，Western blot法测定nNOS、NOS1AP、总体和亚硝基化Dexras1的表达；免疫共沉淀法检测nNOS-NOS1AP共表达；测定脊髓NO含量。 结果 与C组比较，R组T1-3时MWT降低，TWL缩短，脊髓nNOS、NOS1AP及其mRNA表达上调，nNOS-NOS1AP共表达和NO生成增加，亚硝基化Dexras1表达上调(P<0.05)，C＋Z组上述各指标差异无统计学意义(P>0.05)；与R组比较，R＋Z组T1-3时MWT升高，TWL延长，脊髓nNOS-NOS1AP共表达和NO生成减少，亚硝基化Dexras1表达下调(P<0.05)，nNOS、NOS1AP及其mRNA表达差异无统计学意义(P>0.05)；4组间脊髓Dexras1及其mRNA表达差异无统计学意义(P>0.05)。 结论 瑞芬太尼诱发大鼠痛觉过敏的机制可能与上调脊髓nNOS和NOS1AP的表达，促进二者相互作用，介导NO生成和Dexras1亚硝基化修饰有关。 Objective To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats. Methods Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups (n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg-1·min-1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min-1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg-1·min-1 and remifentanil 1.0 μg·kg -1·min-1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R (P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z (P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated (P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z (P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups (P>0.05). Conclusions The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.

    瑞芬太尼痛觉过敏一氧化氮合酶Ⅰ型一氧化氮合酶1衔接蛋白

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    乳酸脱氢酶在小鼠糖尿病神经病理性痛中的作用：与PGC-1α的关系

    王福宇金哲潘文燕向瀚民...
    71-75页
    查看更多>>摘要：目的 评价乳酸脱氢酶在小鼠糖尿病神经病理性痛(DNP)中的作用及其与过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)的关系。 方法 SPF级健康雄性C57BL/6J小鼠，6～8周龄，体质量18～22 g，采用腹腔注射链脲佐菌素120 mg/kg的方法制备小鼠糖尿病模型。取糖尿病造模成功小鼠24只，采用随机数字表法分为2组(n＝12)：DNP组和DNP＋草氨酸钠组(OXA组)。另取12只同月龄正常小鼠为对照组(C组)。OXA组在糖尿病造模成功后腹腔注射草氨酸钠750 mg/kg，1次/d，持续28 d；C组和DNP组腹腔注射等容量生理盐水。于链脲佐菌素注射前3 d、注射后1、2、3和4周(T0-4)时测定小鼠右侧后足机械缩足反应阈(MWT)、血糖和体质量。最后一次行为学测试完成后，麻醉小鼠后眼眶采集血样，测定血清乳酸浓度，随后处死取大脑前额叶皮质组织，测定乳酸含量，采用JC-1法检测线粒体膜电位，DHE探针检测ROS含量，采用Western blot法检测组蛋白乳酸化修饰水平及PGC-1α表达。 结果 与C组比较，DNP组和OXA组T2-4时MWT降低，血清乳酸浓度、前额叶皮质组织乳酸、ROS含量和组蛋白乳酸化修饰水平升高，线粒体膜电位降低，PGC-1α表达下调(P<0.05)；与DNP组比较，OXA组小鼠血糖与体质量差异无统计学意义(P>0.05)，T2-4时MWT升高，血清乳酸浓度、前额叶皮质组织乳酸、ROS含量和组蛋白乳酸化修饰水平降低，线粒体膜电位增加，PGC-1α表达上调(P<0.05)。 结论 乳酸脱氢酶促进小鼠DNP形成发展，其机制与促进前额叶皮质组蛋白乳酸化修饰水平增高及下调PGC-1α表达有关。 Objective To evaluate the role of lactate dehydrogenase in diabetic neuropathic pain (DNP) and the relationship with peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in mice. Methods SPF-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were used to establish diabetes mellitus model by intraperitoneal injection of streptozotocin (STZ) 120 mg/kg. Twenty-four mice with diabetes mellitus were divided into 2 groups (n=12 each) using a random number table method: DNP group and DNP + oxamate group (OXA group). Another 12 SPF-grade healthy male C57BL/6J mice were selected as control group (C group). In OXA group, oxamate 750 mg/kg was intraperitoneally injected once a day for 28 consecutive days. The equal volume of normal saline was given instead in C group and DNP group. The mechanical paw withdrawal threshold (MWT), blood glucose and body weight were measured at 3 days before STZ injection and at 1, 2, 3 and 4 weeks after STZ injection (T0-4). After the last behavioural test was completed, blood samples were collected from the posterior orbits of anesthetized mice for determination of serum lactate concentrations. The animals were then sacrificed and the tissues from the prefrontal cortex of the brain were taken for determination of lactate content, mitochondrial membrane potential (by the JC-1), content of reactive oxygen species (ROS) (using dihydroethidium probes), and level of histone lactylation and expression of PGC-1α (by Western blot). Results Compared with C group, the MWT was significantly decreased at T2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were increased, the mitochondrial membrane potential was decreased, and the expression of PGC-1α was down-regulated in DNP and OXA groups (P<0.05). Compared with DNP group, no significant change was found in blood glucose and body weight (P>0.05), the MWT was significantly increased at T2-4, the serum lactate concentrations, contents of lactate and ROS and level of histone lactylation were decreased, the mitochondrial membrane potential was increased, and the expression of PGC-1α was up-regulated in OXA group (P<0.05). Conclusions Lactate dehydrogenase promotes the development of DNP, and the mechanism is related to promotion of increase in histone lactfication and down-regulation of PGC-1α expression in the prefrontal cortex of mice.

    乳酸糖尿病神经病变过氧化物酶体增殖物激活受体γ共激活因子1α

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    丙泊酚对慢性睡眠剥夺社交行为障碍大鼠内侧前额叶皮层小清蛋白神经元的影响

    曹玥朱进飘陈婷何梦莹...
    76-79页
    查看更多>>摘要：目的 评价丙泊酚对慢性睡眠剥夺社交障碍大鼠内侧前额叶皮层(mPFC)小清蛋白(PV)神经元的影响。 方法 SPF级健康雄性SD大鼠42只，8周龄，体质量200～250 g，采用随机数字表法分为3组(n＝14)：对照组(Con组)、慢性睡眠剥夺＋自然睡眠组(CSD＋NS组)和慢性睡眠剥夺＋丙泊酚组(CSD＋Pro组)。采用改良多平台水环境法建立大鼠睡眠剥夺模型，每天睡眠剥夺20 h，自然睡眠4 h，连续28 d。CSD＋Pro组于睡眠剥夺后腹腔注射丙泊酚40 mg/kg，连续28 d。Con组和CSD＋NS组腹腔注射等容量10%脂肪乳剂。睡眠剥夺结束后采用三箱社交实验检测大鼠社交行为，采用免疫荧光法检测mPFC区PV阳性神经元数目和神经元周围网络(PNN)密度。 结果 与Con组比较，CSD＋NS组快眼动睡眠百分比、三箱社交实验中嗅探时间偏好系数1和嗅探时间偏好系数2降低，mPFC区PV阳性神经元计数和PNN密度减少(P<0.05)；与CSD＋NS组比较，CSD＋Pro组三箱社交实验中嗅探时间偏好系数1和嗅探时间偏好系数2增加，mPFC区PV阳性神经元计数和PNN密度增加(P<0.05)，快眼动睡眠百分比差异无统计学意义(P>0.05)。 结论 丙泊酚可能增加PV神经元数量和功能，改善睡眠剥夺大鼠社交行为障碍。 Objective To evaluate the effect of propofol on parvalbumin (PV) neurons in the medical prefrontal cortex(mPFC)of rats with social behavior disorders induced by chronic sleep deprivation. Methods Forty-two SPF male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups (n=14 each) using a random number table method: control group (group Con), chronic sleep deprivation plus natural sleep group (group CSD+ NS), and chronic sleep deprivation plus propofol group (group CSD+ Pro). Sleep deprivation model was established by the modified multiple platform method, the rats were placed in the sleep-deprivation tank for 20 h a day (14: 00-10: 00), and allowed to sleep naturally for 4 h (10: 00-14: 00) a day for 28 consecutive days. Propofol 40 mg/kg was intraperitoneally injected for 28 consecutive days after sleep deprivation in CSD+ Pro group. While the equal volume of 10% fat emulsion was given in Con and CSD+ NS groups. After the end of sleep deprivation, a three-box social experiment was used to detect the social behavior of rats, and the number of the PV positive cells and density of the perineuronal network (PNN) in the mPFC area were measured by immunofluorescence. Results Compared with group Con, the pertentage of rapid eye movement sleep and sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly decreased, and the number of the PV positive cells and density of PNN in the mPFC area were decreased in group CSD+ NS (P<0.05). Compared with group CSD+ NS, the sniffing time preference coefficients for the strange rat 1 in the first stage and for the strange rat 2 in the second stage were significantly increased, the number of the PV positive cells and density of PNN in the mPFC area were increased(P<0.05), and no significant change was found in the percentage of the rapid eye movement sleep in group CSD+ Pro. Conclusions Propofol probably increases the number and function of PV neurons in the mPFC and ameliorates sleep deprivation-induced social behavior disorders in sleep-deprived rats.

    二异丙酚睡眠剥夺社交缺陷大脑皮质小白蛋白神经元

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    6%羟乙基淀粉130/0.4电解质注射液用于脑膜瘤切除术患者液体治疗的效果

    常亚玲张宇黄祥李娟...
    80-84页
    查看更多>>摘要：目的 评价6%羟乙基淀粉130/0.4电解质注射液用于脑膜瘤切除术患者液体治疗的效果。 方法 择期行脑膜瘤切除术患者92例，年龄18～64岁，ASA分级Ⅰ级或Ⅱ级，BMI 18～30 kg/m2，性别不限，预计手术时长>3 h。采用随机数字表法将患者分为2组(n＝46)：乳酸钠林格液组(LR组)和羟乙基淀粉组(HES组)。LR组全程静脉输注乳酸钠林格液，HES组静脉输注6%羟乙基淀粉130/0.4电解质注射液，最大剂量不超过50 ml/kg，超出部分以乳酸钠林格液补充。采用目标导向液体治疗，维持SVV<13%，MAP 70～90 mmHg。分别于麻醉诱导前即刻(T0)、液体输注1 000和2 000 ml(T1，2)时、术毕即刻(T3)行动脉血气分析，同时监测血栓弹力图。记录术中电解质紊乱、酸碱平衡失调、凝血功能异常的发生情况和去甲肾上腺素用量。术后3和7 d时随访，记录QoR-15评分。记录术后住院时间、脑水肿、肺水肿和恶心呕吐的发生情况。 结果 LR组和HES组分别有4例和6例因手术时间过长被排除，最终2组分别纳入42例和40例。与LR组比较，HES组T3时血浆Na＋浓度升高，T1-3时血浆Cl－浓度和pH值升高，T2，3时血浆Ca2＋浓度降低，T3时反应时间升高，T2，3时凝血时间升高，最大振幅降低，T1-3时凝固角降低(P<0.05)。2组均未发生电解质紊乱及凝血功能异常。2组术中去甲肾上腺素用量和碱中毒发生率、术后Qor-15评分、住院时间、肺水肿、脑水肿及恶心呕吐发生率比较差异无统计学意义(P>0.05)。 结论 相对于乳酸钠林格液而言，6%羟乙基淀粉130/0.4电解质注射液用于脑膜瘤切除术患者液体治疗的效果无差异。 Objective To evaluate the efficacy of 6% hydroxyethyl starch (HES) 130/0.4 electrolyte solution for fluid therapy in the patients undergoing meningioma resection. Methods Ninety-two American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m2, with expected operation duration>3 h, undergoing elective meningioma resection, were divided into 2 groups (n=46 each) using a random number table method: lactated Ringer′s solution (LR) group and HES group. LR was infused throughout operation in group LR, and 6% HES was intravenously infused in group HES, with the maximum dose not exceeding 50 ml/kg, and the excess part was supplemented with LR. Goal-directed fluid therapy was used to maintain stroke volume variation<13% and mean arterial pressure 70-90 mmHg. Arterial blood gas analysis was performed immediately before anesthesia induction (T0), when 1 000 and 2 000 ml of fluid were infused (T1, 2), and at the end of surgery (T3) to record electrolyte and acid-base balance indexes. Thromboelastogram was simultaneously monitored. The occurrence of electrolyte disorder, acid-base imbalance and abnormal coagulation function and consumption of norepinephrine were recorded. Patients were followed up at 3 and 7 days after surgery, and the Chinese quality of recovery-15 scores were recorded. The hospitalization time and occurrence of brain edema, pulmonary edema, nausea and vomiting were recorded. Results In group L and group H, 4 cases and 6 cases were excluded due to prolonged operation time, and 42 cases and 40 cases were finally included, respectively. Compared with LR group, the plasma Na+ concentration was significantly increased at T3, the plasma Cl- concentration and pH value were increased at T1-3, the plasma Ca2+ concentration was decreased at T2, 3, reaction time was increased at T3, coagulation time was increased and maximum amplitude was decreasedat T2, 3, and coagulation Angle was decreased at T1-3(P<0.05). No electrolyte disorder and abnormal coagulation function was found in the two groups. There was no statistically significant difference in the consumption of norepinephrine, postoperative Chinese quality of recovery-15 score, length of hospital stay and incidence of alkalosis, pulmonary edema, brain edema, and nausea and vomiting between the two groups (P>0.05). Conclusions The efficacy of liquid therapy is comparable between HES and LR in the patients undergoing meningioma resection.

    羟乙基淀粉脑膜瘤补液疗法

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    OSGEP在小鼠肝缺血再灌注损伤中的作用：与氧化应激反应的关系

    张藤娟周婉晴陈诚张倩...
    85-90页
    查看更多>>摘要：目的 评价O型唾液酸糖蛋白内肽酶(OSGEP)在小鼠肝缺血再灌注损伤中的作用及其与氧化应激反应的关系。 方法 实验Ⅰ　SPF级健康雄性C57BL/6小鼠24只，野生型12只和OSGEP敲减型12只，6～8周龄，体质量18～22 g，采用随机数字表法分为4组(n＝6)：野生型假手术组(Sham组)、野生型HIRI组(HIRI组)、敲减OSGEP＋假手术组(Sham＋KD组)和敲减OSGEP＋HIRI组(HIRI＋KD组)。阻断肝动脉与肝门静脉60 min恢复灌注的方法制备缺血再灌注损伤模型，Sham组和Sham＋KD组仅暴露血管，不进行夹闭；HIRI组和HIRI＋KD组夹闭60 min恢复灌注。于再灌注6 h后处死小鼠提取肝组织标本，HE染色后光学显微镜下观察病理学结果进行Suzuki评分，检测血清ALT和AST浓度，DCFH-DA荧光探针法检测ROS水平，比色法测定肝组织MDA和谷胱甘肽(GSH)含量，采用Western blot法检测OSGEP表达水平。实验Ⅱ　将生长良好的AML12细胞采用随机数字表法分为4组(n＝30)：对照组(C组)、氧糖剥夺/复糖复氧组(OGD/R组)、氧糖剥夺/复糖复氧组＋敲减OSGEP组(OGD/R＋KD组)和氧糖剥夺/复糖复氧＋敲减OSGEP阴性对照组(OGD/R＋NC组)。C组在正常条件下培养，OGD/R组氧糖剥夺6 h后复糖复氧24 h，OGD/R＋KD组先构建稳定转染OSGEP的AML12细胞，余同OGD/R组。采用CCK-8法检测细胞存活率，检测LDH释放量，DCFH-DA法检测ROS水平，比色法测定MDA和GSH含量。 结果 实验Ⅰ　与Sham组比较，HIRI组OSGEP表达下调，血清AST和ALT浓度、Suzuki评分、肝组织ROS水平和MDA含量升高，GSH含量降低(P<0.05)，Sham＋KD组各指标差异无统计学意义(P>0.05)；与HIRI组比较，HIRI＋KD组血清AST和ALT浓度、Suzuki评分、肝组织ROS水平和MDA含量升高，GSH含量降低(P<0.05)。实验Ⅱ　与C组比较，OGD/R组OSGEP表达下调，细胞存活率和GSH含量降低，LDH释放量、ROS水平和MDA含量升高(P<0.05)；与OGD/R组比较，OGD/R＋KD组细胞存活率和GSH含量降低，LDH释放量、ROS水平和MDA含量升高(P<0.05)，OGD/R＋NC组各指标差异无统计学意义(P>0.05)。 结论 OSGEP在小鼠肝缺血再灌注损伤中通过抑制氧化应激反应发挥内源性保护作用。 Objective To evaluate the role of O-sialoglycoprotein endopeptidase (OSGEP) in hepatic ischemia-reperfusion injury (HIRI) and the relationship with oxidative stress in mice. Methods Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, 12 wild-type and 12 OSGEP knockdown, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups (n=6 each) by the random number table method: wild-type shamoperation group (Sham group), wild-type HIRI group (HIRI group), OSGEP knockdown+ sham operation group (Sham+ KD group) and OSGEP knockdown+ HIRI group (HIRI+ KD group). Ischemia-reperfusion model was prepared by blocking the hepatic artery and portal vein for 60 min followed by reperfusion in anesthetized animals, the blood vessels were only exposed without occlusion in Sham group and Sham+ KD group, and the blood vessels were clamped for 60 min followed by reperfusion in HIRI group and HIRI+ KD group. The mice were sacrificed after 6-h reperfusion to extract liver tissue samples for microscopic examination of histopathological changes (with an optical microscope after HE staining) which were evaluated using Suzuki score and for determination of the serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), level of reactive oxygen species (ROS) (using the DCFH-DA fluorescent probe method), contents of malondialdehyde (MDA) and glutathione(GSH) in liver tissues (using a colorimetric method) and expression of OSGEP (using Western blot). Experiment Ⅱ The well-growing AML12 cells were divided into 4 groups (n=30 each) using a random number table method: control group (C group), oxygen-glucose deprivation/restoration (OGD/R) group, OGD/R+ OSGEP knockdown group (OGD/R+ KD group), and OGD/R+ OSGEP knockdown negative control group (OGD/R+ NC group). Group C was cultured under normal conditions. Group OGD/R was subjected to O2-glucose deprivation for 6 h followed by restoration of O2-glucose supply for 24 h in OGD/R group. In OGD/R+ KD group, stable transfection of AML12 cells with OSGEP knockdown was performed prior to the experiment, and the other procedures were the same as those previously described. The cell survival rate was measured by the CCK-8 assay, the release of lactate dehydrogenase (LDH) was measured, the DCFH-DA method was used to detect the levels of ROS, and the contents of MDA and GSH were determined using a colorimetric method. Results Experiment Ⅰ Compared with Sham group, the expression of OSGEP was significantly down-regulated, the serum concentrations of AST and ALT, Suzuki score, levels of ROS and content of MDA were increased, and the GSH content was decreased in HIRI group (P<0.05), and no significant change was found in each parameter in Sham+ KD group (P>0.05). Compared with HIRI group, the serum concentrations of AST and ALT, Suzuki score, levels of ROS and content of MDA were significantly increased, and the GSH content was decreased in HIRI+ KD group (P<0.05). Experiment Ⅱ Compared with group C, the expression of OSGEP was significantly down-regulated, the cell survival rate and GSH content were decreased, and the release of LDH, levels of ROS and content of MDA were increased in group OGD/R (P<0.05). Compared with OGD/R group, the cell survival rate and GSH content were significantly decreased, and the release of LDH, levels of ROS and content of MDA were increased in OGD/R+ KD group (P<0.05), and no significant change was found in each parameter in OGD/R+ NC group (P>0.05). Conclusions OSGEP plays an endogenous protective role in HIRI by inhibiting oxidative stress in mice.

    内肽酶类肝再灌注损伤氧化性应激

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    ROS在吡那地尔后处理减轻大鼠心肌细胞缺氧复氧损伤中的作用：与Nrf2-ARE信号通路的关系

    周雯静徐鹏陈伟喻田...
    91-96页
    查看更多>>摘要：目的 评价ROS在吡那地尔后处理减轻大鼠心肌细胞缺氧复氧损伤中的作用及其与核因子E2相关因子2(Nrf2)-抗氧化反应元件(ARE)信号通路的关系。 方法 分离、培养成年大鼠心肌细胞，采用随机数字表法分为4组(n＝20)：对照组(C组)、缺氧复氧组(H/R组)、吡那地尔后处理组(P组)和活性氧清除剂N-(2-巯基丙酰基)-甘氨酸(MPG)＋吡那地尔后处理组(MPG＋P组)。C组持续于37 ℃ 95%O2＋5%CO2培养箱中持续培养105 min；缺氧复氧损伤模型制备：5%CO2＋1%O2＋94%N2条件下缺氧45 min，复氧60 min；P组缺氧45 min，吡那地尔50 μmol/L处理5 min，复氧60 min；MPG＋P组缺氧45 min，MPG 2 mmol/L处理10 min，吡那地尔处理5 min，复氧60 min。于复氧末检测心肌细胞Ca2＋含量和Nrf2活性；观察心肌细胞超微结构，并行线粒体Flameng评分；采用Western blot法和RT-PCR法分别检测Nrf2、超氧化物歧化酶1(SOD1)、醌氧化还原酶1(NQO1)和血红素加氧酶1(HO-1)及其mRNA的表达。 结果 与C组比较，H/R组心肌细胞Ca2＋含量、Nrf2活性和Flameng评分升高，Nrf2、SOD1、NQO1和HO-1及其mRNA表达下调(P<0.05)，心肌细胞超微结构损伤加重；与H/R组比较，P组心肌细胞Ca2＋含量和Flameng评分降低，Nrf2活性升高，Nrf2、SOD1、NQO1和HO-1及其mRNA表达上调(P<0.05)，心肌细胞超微结构损伤减轻；与P组比较，MPG＋P组心肌细胞Ca2＋含量和Flameng评分升高，Nrf2活性降低，Nrf2、SOD1、NQO1和HO-1及其mRNA表达下调(P<0.05)，心肌细胞超微结构损伤加重。 结论 ROS参与了吡那地尔后处理减轻大鼠心肌细胞缺氧复氧损伤的过程，与激活Nrf2-ARE信号通路有关。 Objective To evaluate the role of reactive oxygen species (ROS) in attenuation of hypoxia-reoxygenation (H/R) injury in rat cardiomyocytes by pinacidil postconditioning and the relationship with nuclear factor erythrid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway. Methods Adult rat cardiomyocytes were isolated and cultured and then divided into 4 groups (n=20 each) by a random number table method: control group (group C), H/R group, pinacidil postconditioning group (group P) and reactive oxygen scavenger N-(2-mercaptopropionyl)-glycine(MPG)+ pinacidil postconditioning group (group MPG+ P). Group C was continuously exposed to 95%O2+ 5%CO2 in an incubator at 37 ℃ for 105 min. The cells were exposed to 5%CO2+ 1%O2+ 94%N2 in an incubator at 37 ℃ for 45 min followed by reoxygenation for 60 min to prepare H/R injury model. The cells were exposed to hypoxia for 45 min and then treated with pinacidil 50 μmol/L for 5 min followed by reoxygenation for 60 min in group P. The cells were exposed to hypoxia for 45 min, treated with MPG 2 mmol/L for 10 min, and then treated with pinacidil for 5 min followed by reoxygenation for 60 min in group MPG+ P. The content of Ca 2+ and activity of Nrf2 in cardiomyocytes were measured at the end of reoxygenation. The ultrastructure of cardiomyocytes was observed, and mitochondrial ultrastructure was evaluated using mitochondrial Flameng score. The expression of Nrf2, superoxide dismutase (SOD1), quinone oxidoreductase 1 (NQO1), and heme oxygenase 1 (HO-1) protein and mRNA was detected using Western blot and real-time polymerase chain reaction. Results Compared with group C, the Ca2+ content, Nrf2 activity and mitochondrial Flameng score were significantly increased, the expression of Nrf2, SOD1, NQO1 and HO-1 protein and mRNA was down-regulated (P<0.05), and the damage to the ultrastructure of cardiomyocytes was aggravated in group H/R. Compared with H/R group, the Ca2+ content and mitochondrial Flameng score were significantly decreased, the Nrf2 activity was increased, the expression of Nrf2, SOD1, NQO1 and HO-1 protein and mRNA was up-regulated (P<0.05), and the damage to the ultrastructure of cardiomyocytes was attenuated in P group. Compared with P group, the Ca2+ content and mitochondrial Flameng score were significantly increased, the Nrf2 activity was decreased, the expression of Nrf2, SOD1, NQO1 and HO-1 protein and mRNA was down-regulated (P<0.05), and the damage to the ultrastructure of cardiomyocytes was aggravated in MPG+ P group. Conclusions ROS is involved in attenuation of H/R injury by pinacidil postconditioning, which is associated with activation of the Nrf2-ARE signaling pathway in rat cardiomyocytes.

    活性氧吡那地尔缺血后处理肌细胞,心脏低氧NF-E2相关因子2抗氧化反应元件

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    Nrf2/HO-1信号通路在人脐带间充质干细胞来源的外泌体减轻小鼠肾缺血再灌注损伤中的作用

    魏华锋李灵玉罗豪王浩...
    97-103页
    查看更多>>摘要：目的 评价核因子E2相关因子2 (Nrf2) /血红素氧化酶-1(HO-1)在人脐带间充质干细胞来源的外泌体(hucMSCs-exo)减轻小鼠肾缺血再灌注损伤中的作用。 方法 培养人脐带间充质干细胞，提取外泌体，通过透射电子显微镜、纳米颗粒跟踪分析和Western blot法进行鉴定。雄性SPF级C57BL/6小鼠36只，体质量20～25 g，取30只小鼠，采用随机数字表法分为5组(n＝6)：假手术组(Sham组)、假手术＋Nrf2抑制剂ML385组(Sham＋ML385组)、肾缺血再灌注组(I/R组)、肾缺血再灌注＋外泌体组(I/R＋EXO组)、肾缺血再灌注＋外泌体＋Nrf2抑制剂ML385组(I/R＋EXO＋ML385组)。采用夹闭两侧肾蒂45 min后再灌注的方法制备肾缺血再灌注损伤模型。Sham＋ML385组和I/R＋EXO＋ ML385组于造模前45 min腹腔注射ML385 30 mg/kg，I/R＋EXO组和I/R＋EXO＋ ML385组于再灌注前15 min尾静脉注射hucMSCs-exo 100 μg。再灌注24 h时检测血清BUN和Cr浓度；取肾组织，观察病理学变化，检测IL-6、TNF-α和MDA含量、SOD活性和ROS水平，分别采用Western blot法和RT-qPCR法检测Nrf2、HO-1及其mRNA的表达。取6只小鼠采用随机数字表法分为2组(n＝3)：假手术组(Sham-IM组)和肾缺血再灌注组(I/R-IM组)，进行VISQUE活体成像观察。 结果 透射电镜下观察外泌体具有典型的杯状形态，纳米颗粒跟踪分析外泌体平均直径96.7 nm，Western blot法检测其表面标志CD9、CD63、TSG101表达阳性。与Sham-IM组比较，I/R-IM组小鼠肾脏荧光强度值升高(P<0.05)。与Sham组比较，I/R组血清BUN和Cr浓度升高，肾组织IL-6、TNF-α、MDA含量和ROS水平升高，SOD活性降低，Nrf2、HO-1及其mRNA表达下调(P<0.05)，肾组织病理损伤加重；Sham＋ML385组血清BUN和Cr浓度比较差异无统计学意义(P>0.05)。与I/R组比较，I/R＋EXO组血清BUN和Cr浓度降低，肾组织IL-6、TNF-α、MDA含量和ROS水平降低，SOD活性升高，Nrf2、HO-1及其mRNA表达上调(P<0.05)，肾组织病理损伤减轻；与I/R＋EXO组比较，I/R＋EXO＋ML385组血清BUN和Cr浓度升高，肾组织IL-6、TNF-α、MDA含量和ROS水平升高，SOD活性降低，Nrf2、HO-1及其mRNA表达下调(P<0.05)，肾组织病理损伤加重。 结论 hucMSCs-exo减轻小鼠肾缺血再灌注损伤的机制可能与激活Nrf2/HO-1信号通路有关。 Objective To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) in reduction of renal ischemia-reperfusion (I/R) injury by the human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes (hucMSCs-exo) in mice. Methods The hucMSCs were cultured, and exosomes were extracted and identified by transmission electron microscopy, nanoparticle tracking analysis and Western blot. Thirty-six male SPF-grade C57BL/6 mice, weighing 20-25 g, were used. Thirty mice were selected and divided into 5 groups (n=6 each) by a random number table method: sham operation group (Sham group), sham operation + Nrf2 inhibitor ML385 group (Sham + ML385 group), renal I/R group (I/R group), renal I/R + exosome group (I/R+ EXO group), and renal I/R + exosome + Nrf2 inhibitor ML385 group (I/R+ EXO+ ML385 group). A model of renal I/R injury was prepared by clamping the bilateral renal pedicles for 45 min followed by perfusion in anesthetized animals. ML385 30 mg/kg was intraperitoneally injected at 45 min before preparing the model in Sham+ ML385 group and I/R+ EXO+ ML385 group, and hucMSCs-exo 100 μg was injected via the tail vein at 15 min before reperfusion in I/R+ EXO group and I/R+ EXO+ ML385 group. Serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations were detected at 24 h of reperfusion. The renal tissues were obtained for examination of the pathological changes and for determination of contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA), superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels and expression of Nrf2 and HO-1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The left 6 mice were allocated to sham operation group (Sham-IM group, n=3) and renal I/R group (I/R-IM group, n=3) by a random number table method for VISQUE in living imaging observation. Results The exosomes showed a typical cup-shaped morphology with a transmission electron microscope, the nanoparticles tracked and analyzed the average diameter of the exosome, with an average diameter of 96.7 nm, and the positive expression of surface markers CD9, CD63 and TSG101 was detected using Western blot. The renal fluorescence intensity value was significantly increased in I/R-IM group as compared with Sham-IM group (P<0.05). Compared with Sham group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated (P<0.05), and the pathological changes of renal tissues were aggravated in I/R group, and no significant change was found in serum BUN and Cr concentrations in Sham+ ML385 group (P>0.05). Compared with I/R group, the serum BUN and Cr concentrations were significantly decreased, the contents of IL-6, TNF-α and MDA and ROS levels were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 protein and mRNA was up-regulated (P<0.05), and the pathological changes of renal tissues were significantly attenuated in I/R+ EXO group. Compared with I/R+ EXO group, the serum BUN and Cr concentrations were significantly increased, the contents of IL-6, TNF-α and MDA and ROS levels were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 protein and mRNA was down-regulated (P<0.05), and the pathological changes of renal tissues were aggravated in I/R+ EXO+ ML385 group. Conclusions The mechanism by which hucMSCs-exo reduces renal I/R injury may be related to activation of the Nrf2/HO-1 signaling pathway in mice.

    外泌体间充质干细胞肾再灌注损伤NF-E2相关因子2血红素加氧酶-1

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