首页|持续静脉泵注利多卡因对脓毒症早期大鼠肾损伤的影响

持续静脉泵注利多卡因对脓毒症早期大鼠肾损伤的影响

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目的 探讨持续静脉泵注利多卡因对脓毒症早期大鼠肾损伤的影响.方法 选择160只SPF级雄性SD大鼠,采用随机数字表法分为4组(每组40只):假手术组(S组)、盲肠结扎穿孔组(CLP组)、利多卡因组(L组)和生理盐水组(N组).S组大鼠打开腹腔后立即缝合,其余组采用盲肠结扎穿孔(CLP)法建立脓毒症模型.L组大鼠建模完成即刻给予利多卡因负荷量10mg/kg,再以10mg·kg-1·h-1持续尾静脉泵注3h;N组给予等体积生理盐水.记录4组大鼠体重;于开腹即刻(T0)、CLP术后2h(T1)、CLP术后4h(T2)、CLP术后8 h(T3)、CLP术后20 h(T4)、CLP术后24 h(T5)时每组各取5只大鼠采用酶联免疫吸附测定(ELISA)法测定血清白细胞介素-6(IL-6)、肿瘤坏死因-α(TNF-α)、肌酐(Cr)、尿素氮(BUN)、胱抑素C(Cys-C)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平,苏木精-伊红(H-E)染色观察T5时肾组织病理学变化情况,收集并测定T1~T5时大鼠尿量;观察各组剩余10只大鼠72 h生存率.结果 4组大鼠体重比较差异无统计学意义(均P>0.05).4组大鼠T0时IL-6、TNF-α、Cr、BUN、Cys-C、NGAL水平差异无统计学意义(均P>0.05).与S组比较:CLP组、L组和N组大鼠T1~T5时IL-6、TNF-α、Cr、BUN、Cys-C、NGAL 水平较高(均P<0.05),尿量较少(均 P<0.05).与 CLP 组比较:L 组大鼠 T1~T5 时 IL-6、TNF-α、Cr、BUN、Cys-C、NGAL水平较低(均P<0.05),尿量较多(均P<0.05);N组大鼠T1、T2时Cr水平较低(均P>0.05),T3~T5时Cr水平差异无统计学意义(均 P>0.05),T1~T5 时 IL-6、TNF-α、BUN、Cys-C、NGAL 水平差异无统计学意义(均 P>0.05),T1时尿量较多(均 P<0.05),T2~T5时尿量差异无统计学意义(均P>0.05).与N组比较:L组大鼠T1~T5时IL-6、TNF-α、Cr、BUN、Cys-C、NGAL水平较低(均P<0.05);T2~T5时尿量较多(均P<0.05),T1时差异无统计学意义(P>0.05).4组大鼠肾组织中肾小球、肾小管及小管间质结构完整,肾皮质、髓质结构清晰,肾单位形态结构正常,基底膜、系膜区均未见炎症细胞浸润.与S组(100%)比较,CLP组(10%)、L组(60%)和N组(40%)大鼠72 h生存率较低(均P<0.05);与CLP组比较,L组大鼠72 h生存率较高(P<0.05);其余各组间大鼠72 h生存率差异无统计学意义(均P>0.05).结论 静脉泵注利多卡因可以抑制IL-6和TNF-α表达,减轻炎症反应,减少脓毒症大鼠早期肾损伤,起到肾保护的作用.
Effect of continuous intravenous infusion of lidocaine on early renal injury in septic rats
Objective To investigate the effect of continuous intravenous infusion of lidocaine on early renal injury in septic rats.Methods A total of 160 SPF-grade male SD rats were divided into four groups(n=40)using the random number table method:group sham(group S),group cecal ligation and puncture(group CLP),group lidocaine group(group L),and group normal saline group(group N).In group S,the rats underwent laparotomy followed by immediate suturing,while the other groups underwent cecal ligation and puncture(CLP)to establish a sepsis model.Immediately after modeling,group L group received a loading dose of 10 mg/kg lido-caine,followed by continuous intravenous infusion of lidocaine via the tail vein at 10 mg·kg1·h-1 for 3 h.Group N received the same volume of normal saline.The body weight of rats in all four groups was recorded.Their levels of serum interleukin-6(IL-6),tumor necro-sis factor-α(TNF-α),creatinine(Cr),blood urea nitrogen(BUN),cystatin C(Cys-C),and neutrophil gelatinase-associated lipocalin(NGAL)were measured using enzyme-linked immunosorbent assay(ELISA)immediately after laparotomy(T0),at post-CLP 2 h(T1),at post-CLP 4 h(T2),at post-CLP 8 h(T3),at post-CLP 20 h(T4),and at post-CLP 24 h(T5).The histopathological changes in kidney tissue at T5 were observed by hematoxylin-eosin(H-E)staining,and urine volume was measured from T,to T5.The 72-hour survival rates of the remaining 10 rats in each group were also observed.Results There was no statistical difference in body weight among the four groups(all P>0.05).At T0,no statistical differences were found in the levels of IL-6,TNF-α,Cr,BUN,Cys-C,and NGAL among the four groups(all P>0.05).Compared with group S,groups CLP,L,and N showed increases in the levels of IL-6,TNF-α,Cr,BUN,Cys-C,and NGAL and decreases in urine volume from T,to T5(all P<0.05).Compared with group CLP,group L presented decreases in the lev-els of IL-6,TNF-α,Cr,BUN,Cys-C,and NGAL and increases in urine volume from T1 to T5(all P<0.05);group N showed reduced Cr levels at T,and T2(all P<0.05),without statistical difference from T3 to T5(all P>0.05);there were no statistical differences in the levels of IL-6,TNF-α,BUN,Cys-C,and NGAL from T1to T5(all P>0.05);urine volume increased at T,(P<0.05),without statistical differenc-es from T2 to T5(all P>0.05).Compared with group N,group L showed decreases in the levels of IL-6,TNF-α,Cr,BUN,Cys-C,and NGAL from T1to T5(all P<0.05),and increases in urine volume from T2 to T5(all P<0.05),though the difference at T1 was not statistical-ly significant(P>0.05).In all four groups,the kidney tissue showed intact glomeruli,renal tubules,and interstitial structures,with clear cortical and medullary structures.The morphology of the nephron was normal,without inflammatory cell infiltration observed in the basement membrane or mesangial area.Compared with group S(100%),group CLP(10%),group L(60%)and group N(40%)had a de-creased 72-hour survival rate(all P<0.05);Compared with the CLP group,group L showed an increased 72-hour survival rate(P<0.05);there were no statistical differences in 72-hour survival rate among the other groups(all P>0.05).Conclusions Intravenous infusion of lidocaine can inhibit the expression of IL-6 and TNF-α,relieve inflammation,and alleviate early renal injury in septic rats,providing protective effect on the kidneys.

SepsisInflammatory factorAcute kidney injuryLidocaine

张贵超、张宇轩、李青青、徐桂萍

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石河子大学研究生院,石河子 832003

新疆维吾尔自治区人民医院麻醉科,新疆麻醉管理临床医学研究中心,乌鲁木齐 830001

脓毒症 炎症因子 急性肾损伤 利多卡因

2024

国际麻醉学与复苏杂志
中华医学会,徐州医学院

国际麻醉学与复苏杂志

CSTPCD
影响因子:0.909
ISSN:1673-4378
年,卷(期):2024.45(11)