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中华内分泌代谢杂志
中华内分泌代谢杂志

宁光

月刊

1000-6699

cjem@vip.163.com

021-64315587

200025

上海市瑞金二路197号

中华内分泌代谢杂志/Journal Chinese Journal of Endocrinology and MetabolismCSCD北大核心CSTPCD
查看更多>>1985年创刊，中华医学会主办。本刊是反映我国当代及与国外合作的，在内分泌代谢病学领域内临床与科研最新成果的高级学术刊物。在强调刊文的先进性、科学性与新颖性的同时，也十分重视临床的实用性和论文的可读性。本刊设指南与共识、述评、专论、论坛、临床研究、基础研究、综述、讲座、临诊应对、当年学术进展与动态、临床经验交流、新药研究、学术争鸣及国外期刊论文评论等栏目。本刊的读者对象主要为各级从事临床和基础内分泌代谢病学工作的医、教、研人员及研究生，以及内、外、儿、妇科以及神经、泌尿、老年、营养等相关科室的人员。
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    《糖尿病患者足溃疡预防指南(IWGDF2023更新)》解读与应用

    柳岚车建芳崔悦孙金姗...
    1-4页
    查看更多>>摘要：足溃疡预防是降低糖尿病患者截肢率的重要一环。关于糖尿病足溃疡的预防，国际糖尿病足工作组2023年指南与其2019年指南有着很大的不同，最主要的变化是对各条推荐意见补充了高级别的证据内容(大多为随机对照研究的结果)；主张将局部皮温测定、参加足踝运动训练和心理干预等用于足病的预防。本文从识别高危足、定期检查高危足、健康教育、确保日常穿着合适鞋、治疗溃疡危险因素以及综合足部护理这6个方面对2版指南进行比较；并结合临床，对2023年版指南在中国的应用进行分析和展望。 Foot ulcer prevention plays a crucial role in reducing the amputation rate among diabetic patients. With regard to the prevention of diabetic foot ulcers, the 2023 guidelines of the International Working Group of Diabetic Foot(IWGDF) were different from the 2019 counterpart. The most notable change is the addition of high-level evidence to support recommendations, primarily derived from randomized controlled studies. The 2023 guidelines also advocate for local skin temperature measurement, participation in ankle exercise training, and psychological intervention for foot ulcer prevention. This article conducts a comparative analysis of the two guidelines across six key dimensions: identification of high-risk feet, regular examination of high-risk feet, health education, ensuring appropriate daily footwear, addressing ulcer risk factors, and comprehensive foot care. Drawing from clinical insights, the application and prospective implications of the 2023 guidelines in China are also examined.

    糖尿病足溃疡预防

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    三例成年发生的特发性低促性腺激素性性腺功能减退症的诊疗特点分析

    骆静蒲美岑黄奕娟王丹...
    5-10页
    查看更多>>摘要：目的 探讨成年发生的特发性低促性腺激素性性腺功能减退症(AIHH)的诊疗特点并提供诊疗思路。 方法 收集就诊于南方医科大学南方医院内分泌代谢科的3例男性AIHH患者的临床、实验室、影像学及完整随访资料。 结果 3例患者均为男性，平均年龄39(22～40)岁，2例以"乳房增大，性功能下降"为主诉入院，1例以"性功能下降"为主诉入院。体格检查：阴茎长度6(5～6)cm，双侧睾丸体积7.96(4.70～8.82)mL；基础性激素水平：睾酮0.32(0.24～2.96)ng/mL、卵泡刺激素0.56(0.1～0.75)mIU/mL、黄体生成素0.69(0.1～1.03)mIU/mL；垂体前叶分泌的其他激素水平未见异常；下丘脑-垂体区域磁共振成像(MRI)提示其中1例患者存在垂体微腺瘤。3例患者选择促性腺激素释放激素(GnRH)脉冲泵或促性腺激素序贯治疗，1例患者在使用GnRH脉冲泵治疗后下丘脑-垂体-性腺(HPG)轴功能逆转并持续1年，但随后仍不可逆性降低。 结论 AIHH同时具有成年起病及特发性低促性腺激素的特点，生育力改善仍是此类患者的重要需求，GnRH脉冲泵或促性腺激素治疗对AIHH患者具有良好的治疗效果但疗效具有波动性，应及时进行生育力保存。 Objective To investigate the clinical characteristics and offer diagnostic and therapeutic approaches for adult-onset idiopathic hypogonadotropic hypogonadism(AIHH). Methods Clinical, laboratory, and imaging data, as well as follow-up information, of three male patients diagnosed with AIHH at the Department of Endocrinology and Metabolism of Nanfang Hospital, Southern Medical University, were systematically reviewed and analyzed. Results All three patients were male, with a median age of 39 years(range, 22 to 40). Two patients reported symptoms of enlarged breasts and reduced sexual function, while one case solely reported a decline in sexual function. Physical examination showed that the median length of the penis was 6 cm(range, 5 to 6 cm), and the bilateral testicular volume was 7.96 mL(4.70-8.82 mL). Basal hormone levels at the time of initial visit to our hospital as follows: the median testosterone level was 0.32 ng/mL(0.24-2.96 ng/mL), median follicle stimulating hormone(FSH) level was 0.56 mIU/mL(0.1-0.75 mIU/mL), and the median luteinizing hormone(LH) level was 0.69 mIU/mL(0.1-1.03 mIU/mL). The levels of other hormones secreted by the anterior pituitary gland were normal. Hypothalamic-pituitary magnetic resonance imaging(MRI) showed that 1 patient had a pituitary microadenoma. Three patients were treated with pulsatile GnRH or gonadotropins, one of which had hypothalamic-pituitary-gonadal(HPG) axis function reversal after GnRH pulse pump therapy and lasted for 1 year, but then still had irreversible reduction. Conclusion AIHH is marked by adult-onset disease and idiopathic hypogonadism. Enhancing fertility remains a critical requirement for these patients. Pulsatile GnRH treatment or gonadotropin therapy, as viable treatments, exhibit therapeutic effects, albeit with occasional fluctuations. Therefore, the emphasis lies in the timely consideration of fertility preservation.

    成年发生特发性低促性腺激素性性腺功能减退生精治疗生育力保存

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    布罗索尤单抗治疗儿童X连锁低磷性佝偻病疗效评估

    方韶晗邓芳袁悦李旭...
    11-16页
    查看更多>>摘要：目的 评估布罗索尤单抗在X连锁低磷性佝偻病患儿中应用的有效性及安全性。 方法 回顾性分析2021年11月至2023年9月在安徽省儿童医院儿童肾脏科住院确诊的9例X连锁低磷性佝偻病并接受布罗索尤单抗治疗患儿的临床资料，包括患儿一般情况、临床表现、辅助检查、布罗索尤单抗治疗及随访情况等。 结果 9例患儿中男性5例，女性4例，确诊中位年龄为2岁，传统治疗后血磷波动在0.7～0.9 mmol/L。开始使用布罗索尤单抗治疗中位年龄为2.8岁，药物初始使用剂量为0.8 mg/kg，每2周皮下注射1次。布罗索尤单抗治疗6个月后实验室及影像学指标得到改善，1个月后血磷从开始平均(0.81±0.14)mmol/L上升到(1.02±0.10)mmol/L(t＝3.85, P＝0.001)，6个月后上升到(1.14±0.25)mmol/L(t ＝3.58, P＝0.002)。碱性磷酸酶(ALP)由治疗前平均(509.89±110.10)U/L，1个月后下降到(447.89±106.76)U/L(t＝1.21, P＝0.243)，6个月后ALP显著下降到(385.89±60.33)U/L(t＝2.96, P＝0.009)。身高百分位由治疗前平均18.42±10.09到6个月后26.56±16.59(t＝1.26, P＝0.227)。双下肢佝偻病严重程度评分由治疗前平均(4.61±1.36)分到6个月后的(3.06±1.51)分(t＝2.29, P＝0.036)。治疗期间未出现严重不良事件。 结论 布罗索尤单抗治疗X连锁低磷性佝偻病安全、有效，不良反应少，具有良好的临床应用价值。 Objective To evaluate the efficacy and safety of Burosumab in patients with X-linked hypophosphatemic rickets. Methods Clinical data of 9 children diagnosed with X-linked hypophosphatemic rickets and treated with Burosumab in the Department of Pediatric Nephrology, Anhui Children′s Hospital from November 2021 to September 2023 were retrospectively analyzed, including the general information, clinical manifestations, auxiliary examination, Burosumab treatment and follow-up. Results Among the 9 cases, there were 5 males and 4 females, with a median age at diagonosis of 2 years. After traditional treatment, the fluctuation of serum phosphorus ranged from 0.7 to 0.9 mmol/L. The median age at the initiation of Burosumab treatment was 2.8 years, and the initial dosage was 0.8 mg/kg, administrated subcutaneously every 2 weeks. The laboratory and imaging indexes were improved after 6 months of Burosumab treatment, and the mean serum phosphorus level increased from(0.81±0.14) mmol/L to(1.02±0.10) mmol/L at 1 month(t=3.85, P=0.001) and(1.14±0.25) mmol/L at 6 months(t=3.58, P=0.002). The average alkaline phosphatase(ALP) level decreased from(509.89±110.10) U/L before treatment to(447.89±106.76) U/L after 1 month(t=1.21, P=0.243). After 6 months, the ALP level significantly decreased to(385.89±60.33) U/L (t=2.96, P=0.009). The average height percentile increased from 18.42±10.09 before treatment to 26.56±16.59 after 6 months(t=1.26, P=0.227). Rachitis severity scores of both lower limbs ranged from 4.61±1.36 before treatment to 3.06±1.51 after 6 months(t=2.29, P=0.036). No serious adverse events occurred during treatment. Conclusion Burosumab is safe and effective in treating X-linked hypophosphatemic rickets, exhibiting minimal side effects and significant clinical applicability value.

    X连锁低磷性佝偻病儿童布罗索尤单抗疗效

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    幼儿期应用布罗索尤单抗治疗X连锁低磷性佝偻病一例随访18个月分析

    王小红陈琼杨海花王会贞...
    17-21页
    查看更多>>摘要：目的 回顾性分析1例X连锁低磷性佝偻病患儿幼儿期应用布罗索尤单抗治疗18个月的临床资料，提高临床医生对该药安全性和有效性的认识。 方法 收集患儿临床资料，经父母同意后行全外显子基因检测确诊为X连锁低磷性佝偻病。给予布罗索尤单抗治疗18个月，每11～14 d检测空腹血磷、血钙、碱性磷酸酶、计算钙磷乘积，每2～6周检测甲状旁腺激素、25-羟维生素D，每3个月测定膝间距、肝肾功能、尿钙/尿肌酐、心电图等，每6个月进行影像学检查，持续对患儿进行随访。 结果 全外显子测序结果显示患儿X染色体上与内肽酶同源的磷酸盐调节基因(PHEX)存在c.1080_1081insCAATGTTA(p.T361Qfs*3)自发杂合移码突变，既往未见报道。患儿应用布罗索尤单抗治疗18个月，生化指标明显改善，佝偻病评分降低，无牙龈脓肿及其他不良反应发生。 结论 PHEX基因c.1080_1081insCAATGTTA(p.T361Qfs*3)变异为该患儿致病原因，布罗索尤单抗作为X连锁低磷性佝偻病靶向治疗药物，治疗疗效明显。 Objective To retrospectively analyze a pediatric case of X-linked hypophosphatemic rickets treated with Burosumab and improve clinicians′ awareness of the safety and effectiveness of the drug. Methods Clinical data of the child were collected. Whole-exon genetic testing after parental consent confirmed X-linked hypophosphatemic rickets. During 18 months of Burosumab treatment, fasting blood phosphorus, alkaline phosphate, calcium, and calcium phosphate product were monitored every 11-14 days. Parathyroid hormone and 25 hydroxyvitamin D were checked every 2-6 weeks, while knee spacing, liver and kidney function, urinary calcium creatinine ratio, electrocardiogram were assessed every 3 months. Radiological imaging was performed every 6 months, with continuous follow-up of the child. Results Whole-exon sequencing results showed a c. 1080_1081insCAATGTTA(p.T361Qfs*3) spontaneous heterozygous frameshift mutation in the PHEX gene in the child, which has not been reported previously. After the patient was treated with Burosumab for 18 months, the biochemical indexes were significantly improved, and the rickets score was reduced, without gingival abscess or other adverse events. Conclusion The variant c. 1080_1081insCAATGTTA(p.T361Qfs*3) in the PHEX gene was identified as the cause of the patient′s condition. Burosumab, as a targeted therapeutic agent for X-linked hypophosphatemic rickets, showed significant treatment efficacy.

    布罗索尤单抗低磷性佝偻病PHEX基因空腹血磷

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    绝经前后空腹血糖水平的变化：基于开滦体检队列的研究

    张亚亚代巧云吴寿岭陈朔华...
    22-29页
    查看更多>>摘要：目的 分析绝经前后空腹血糖水平的变化趋势。 方法 采用队列研究的方法，以参加开滦体检队列首次体检并在第7次体检结束时获得绝经年龄的≥18岁女性为研究对象，共纳入3 749例女性的22 057人次体检记录进行分析。将空腹血糖(FPG)进行自然对数转换，采用分段线性混合效应模型方法分析绝经前后lnFPG的变化，进一步分析基线年龄和基线体重指数(BMI)与绝经前后时间对lnFPG的相乘交互作用。 结果 本研究女性的首次体检平均年龄为(45.63±4.52)岁，中位绝经年龄为51(50～53)岁，体检次数的中位数为6(5～7)次。分段线性混合效应模型结果显示，LnFPG从绝经前1年开始增加，平均年增长量为0.021 mmol/L；在绝经至绝经后5年持续增加，平均年增长量降为0.007 mmol/L；在绝经5年以后，LnFPG趋于平稳。基线年龄会影响lnFPG在绝经前后的变化，基线年龄≥45岁与绝经前6年至绝经前1年的时间分段对lnFPG有负向交互作用(P＝0.032)，基线年龄≥45岁的女性在绝经前1年至绝经后5年，LnFPG的年平均增长量均高于基线年龄<45岁的女性(均P<0.05)。基线BMI与绝经前后时间对lnFPG有正向相乘交互作用，即肥胖女性在绝经前6年至绝经前1年和绝经至绝经后5年这2个时间分段，LnFPG的年平均增长量均高于基线BMI<24 kg/m2的女性(均P<0.05)。 结论 绝经对FPG会产生不良影响，不良变化主要发生在绝经前1年至绝经后5年，年龄和BMI会影响绝经前后FPG的变化。 Objective To analyze the changes of fasting plasma glucose(FPG)level before and after menopause. Methods Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods. Results The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause(P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause(P<0.05). Conclusions Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.

    绝经空腹血糖队列研究体重指数

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    白细胞介素-36在糖尿病肾病患者中的表达及其对单核细胞功能的调控作用

    李江雁孔亚坤赵建林赵利超...
    30-36页
    查看更多>>摘要：目的 分析白细胞介素-36(IL-36)家族成员在糖尿病肾病(diabetic kidney disease, DKD)外周血中的水平，探讨重组人IL-36α对DKD患者单核细胞功能的调控作用。 方法 连续入组2型糖尿病患者41例、DKD患者36例、对照者20名，分离血浆和外周血单个核细胞，酶联免疫吸附法检测血浆IL-36α、IL-36β、IL-36γ、IL-36受体拮抗剂(IL-36Ra)水平，分选单核细胞，实时定量PCR检测单核细胞中IL-36受体亚基mRNA表达。使用重组IL-36α刺激单核细胞，检测培养上清中毒性分子和细胞因子水平，流式细胞术检测程序性死亡受体-1(PD-1)和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)表达。单核细胞与Vero细胞共培养，评估单核细胞的杀伤功能。 结果 2型糖尿病组和DKD组血浆IL-36α、IL-36β水平显著高于对照组，DKD组血浆IL-36α水平亦高于2型糖尿病组(P<0.05)。IL-36γ和IL-36Ra水平在3组之间差异无统计学意义(P>0.05)。单核细胞中IL-36受体亚基mRNA表达在3组之间差异无统计学意义(P>0.05)。DKD组肿瘤坏死因子α(TNF-α)水平高于对照组和2型糖尿病组(P<0.05)，PD-1和CTLA-4水平低于对照组和2型糖尿病组(P<0.05)。DKD组单核细胞诱导Vero细胞死亡的比例显著高于对照组和2型糖尿病组(P<0.05)。重组人IL-36α刺激后，DKD患者单核细胞分泌颗粒酶B和TNF-α水平显著升高(P<0.05)，单核细胞诱导Vero细胞死亡的比例显著升高(P＝0.024)。 结论 DKD组单核细胞分泌颗粒酶B和IL-36α水平升高诱导单核细胞功能增强。 Objective To analyze the level of interleukin-36(IL-36) family cytokines in peripheral blood, and explore the regulatory role of recombinant human IL-36α in monocyte function in patients with diabetic kidney disease(DKD). Methods A total of 41 type 2 diabetes mellitus(T2DM) patients, 36 DKD patients, and 20 controls were consecutively enrolled. Plasma and peripheral blood mononuclear cells(PBMCs) were isolated. Enzyme-linked immunosorbent assay(ELISA) was used to measure plasma levels of IL-36α, IL-36β, IL-36γ, and IL-36 receptor antagonist(IL-36Ra). PBMCs were sorted, and real-time quantitative PCR was performed to detect the mRNA expression of IL-36 receptor subunits in monocytes. Monocytes were stimulated with recombinant IL-36α, and levels of cytotoxic molecules and cytokines in the culture supernatant were measured. Flow cytometry was used to assess the expressions of programmed death receptor-1(PD-1) and cytotoxic T-lymphocyte-associated protein 4(CTLA-4). Co-culture of monocytes with Vero cells was performed to evaluate monocyte cytotoxicity. Results Plasma levels of IL-36α and IL-36β in the T2DM and DKD groups were significantly higher than those in the control group. The DKD group also showed higher plasma levels of IL-36α compared to the T2DM group(P<0.05). There were no significant differences in IL-36γ and IL-36Ra levels among the three groups(P>0.05). The mRNA expression of IL-36 receptor subunits in monocytes was comparable among the three groups(P>0.05). The DKD group had higher level of tumor necrosis factor-alpha(TNF-α) compared to the control and T2DM groups(P<0.05). The levels of PD-1 and CTLA-4 were lower in the DKD group than those in the control and T2DM groups(P<0.05). The proportion of monocyte-induced Vero cell death was significantly higher in the DKD group compared to the control and T2DM groups(P<0.05). After stimulation with recombinant human IL-36α, monocytes from DKD patients showed a significant increase in the secretion of granzyme B and TNF-α(P<0.05), as well as an increased proportion of monocyte-induced Vero cell death(P=0.024). Conclusion In DKD patients, elevated IL-36α and granzyme B levels in monocytes enhance monocyte function.

    糖尿病肾病白细胞介素-36单核细胞免疫调控

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    江苏高碘地区碘营养状态变化对老年人群甲状腺功能的影响：一项系列横断面调查

    张梦杰张丽娜密玮诺孙宇...
    37-43页
    查看更多>>摘要：目的 调查水源性高碘地区改水后≥65岁老年人碘营养状态的变化及对老年人甲状腺功能的影响。 方法 选取2015年至2017年我国31省市甲状腺疾病、碘营养和糖尿病的全国流行病学调查(TIDE研究)的江苏徐州姚集镇(水源性高碘地区)调查结果，选取2021年5月至8月对江苏省宿迁顺河镇(碘大于适宜量地区)及徐州姚集镇≥65岁老年人群甲状腺疾病的筛查、监控和干预(TOPS研究)的调查结果。每位受试者均完成问卷调查、体格检查、实验室检测和甲状腺超声检查。最终纳入≥65岁老年人2 717名，其中，组1为TIDE组，258名；组2为TOPS徐州组，1 313名；组3为TOPS宿迁组，1 146名。 结果 组2的尿碘浓度(UIC)显著低于组1[(235.16±67.09)μg/L对(491.58±384.93)μg/L，P<0.001]，但与组3的差异无统计学意义[(235.16±67.09)μg/L对(231.62±66.11)μg/L，P>0.05]。组2的血清促甲状腺素(TSH)水平显著低于组1[(2.92±5.14)μIU/mL对(4.15±9.19)μIU/mL，P<0.001]。与组2和组3相比，组1老年人亚临床甲状腺功能减退症(甲减)的患病率最高(22.48%对10.13%和8.12%，P<0.001)。无论是在高碘地区还是在碘大于适宜量地区，TSH水平均与年龄呈线性相关。随着年龄的增长，TSH水平逐渐升高。 结论 增龄和碘营养状态与老年人TSH水平改变显著相关。高碘地区老年人碘营养状况恢复正常后可显著减少老年人甲减的患病率。 Objective To investigate the alteration in iodine nutritional status and influence on thyroid function in the elderly aged≥65 years following water source modification in high iodine areas. Methods Data from Yaoji Town, Xuzhou, Jiangsu(an area with high iodine due to water sources) of the national epidemiological survey on thyroid diseases, iodine nutrition, and diabetes(TIDE study) in 31 provinces and cities in China from 2015 to 2017 were utilized. Additionally, data from the screening, monitoring, and intervention on thyroid diseases(TOPS study) in the elderly(≥65 years) in Shunhe Town, Suqian, Jiangsu(an area with iodine levels exceeding the recommended amount), and Yaoji Town, Xuzhou from May to August 2021, are included. Each subject completed a questionnaire, physical examination, laboratory tests and thyroid ultrasound examinations. A total of 2 717 subjects aged≥65 years were included, including group 1, 258 subjects in TIDE study Group 2, 1 313 subjects in TOPS Xuzhou area Group 3, 1 146 subjects in TOPS Suqian area. Results The urinary iodine concentration(UIC) in group 2 was significantly lower than that in group 1 [(235.16±67.09)μg/Lvs (491.58±384.93)μg/L,P<0.001], but no significant difference compared with group 3 [(235.16±67.09) μg/Lvs(231.62±66.11) μg/L, P>0.05]. The serum TSH level in group 2 was significantly lower than that in group 1 [(2.92±5.14)μIU/mLvs (4.15±9.19)μIU/mL,P<0.001]. Compared with group 2 and 3, the prevalence of subclinical hypothyroidism in the elderly in group 1 was the highest(22.48%vs 10.13% and 8.12%, P<0.001). TSH levels were linearly correlated with age in both excessive iodine and more than adequate iodine nutrition areas. TSH level was gradually increased with age. Conclusion The alteration in TSH levels among the elderly is notably linked to both aging and iodine status. The prevalence of hypothyroidism in the elderly can be significantly reduced when the iodine nutrition status of the elderly returns to normal.

    碘营养状态碘过量老年人群促甲状腺素甲状腺功能减退

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    长链非编码RNA AW112010通过miR-204/POU2F2轴改善衰老小鼠脂肪细胞的胰岛素抵抗

    王锐王淑文张一凡胡雅琪...
    44-52页
    查看更多>>摘要：目的 探讨长链非编码RNA AW112010(lncRNA AW112010)是否可能通过miR-204/POU类同源盒2(POU2F2)信号通路改善衰老脂肪细胞的胰岛素抵抗。 方法 体内实验：将C57BL/6小鼠按体重分成年轻对照组(4月龄)、衰老模型组(18月龄)；实时荧光定量PCR及Western印迹法检测附睾脂肪组织中lncRNA AW112010、miR-204-5p、POU2F2、衰老相关指标(p16、p21)及胰岛素信号通路基因[胰岛素受体(INSR)、胰岛素受体底物1(IRS1)、磷脂酰肌醇激酶(PI3K)、蛋白激酶B(AKT)]的表达量。体外实验：用阿霉素诱导3T3-L1衰老脂肪细胞模型，β-gal染色观察细胞衰老，成功构建miR-204抑制剂及miR-204模拟物的小干扰RNA，转染3T3-L1脂肪细胞。 结果 实时荧光PCR与Western印迹结果表明，与年轻小鼠比较，衰老小鼠附睾脂肪组织中AW112010的表达水平增高，而miR-204-5p的表达水平降低；衰老小鼠附睾脂肪组织中POU2F2、p16、p21的表达水平增高，而INSR、IRS1、PI3K、GLUT4 mRNA及蛋白的表达水平降低。β-gal染色结果表明，阿霉素诱导的3T3-L1衰老脂肪细胞数量明显增多，且与对照组相比，阿霉素诱导的衰老脂肪细胞中AW112010、POU2F2、p16、p21的表达量增高，而miR-204-5p、INSR、IRS1、PI3K、GLUT4的表达量降低，培养基中葡萄糖的剩余量增多。与对照组相比，miR-204过表达后，衰老指标p16、p21及靶基因POU2F2的表达量降低；INSR、GLUT4的表达量增高。 结论 衰老小鼠脂肪细胞中上调的lncRNA AW112010可能通过靶向miR-204-5p/POU2F2/IRS1导致胰岛素抵抗。 Objective To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway. Methods In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased. Conclusion Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.

    衰老LncRNAAW112010miR-204-5pPOU2F2胰岛素抵抗

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    竹节参总皂苷调控AMPK/mTOR/ULK1通路介导的铁自噬对糖尿病心肌病大鼠心肌细胞铁死亡的抑制作用

    任晓静张海龙程远马媛...
    53-63页
    查看更多>>摘要：目的 探究竹节参总皂苷(TSPJ)对糖尿病心肌病(DCM)大鼠心肌细胞铁死亡的作用及调控机制。 方法 实验1：将SD大鼠分为对照组、DCM组、TSPJ低剂量组、TSPJ高剂量组、二甲双胍组(Met)，每组各10只。实验2：将SD大鼠分为对照组、DCM组、TSPJ组、腺苷酸活化蛋白激酶(AMPK)抑制剂Compound C组、TSPJ＋AMPK激动剂AICAR组，每组各10只。除对照组外，其余各组大鼠均采取腹腔注射链脲佐菌素构建DCM模型。各组大鼠给予对应药物干预8周后，检测各组大鼠体重及糖脂代谢水平；超声心动图检测大鼠心功能指标；酶联免疫吸附(ELISA)法检测各组大鼠血清乳酸脱氢酶(LDH)、心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶MB(CK-MB)水平；苏木精-伊红(HE)染色和电镜观察心肌组织病理变化；试剂盒检测心肌组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)、丙二醛、活性氧簇(ROS)及Fe2＋水平；Western印迹法检测心肌组织铁死亡、铁自噬以及AMPK/哺乳动物雷帕霉素靶蛋白/UNC-51样激酶1(mTOR/ULK1)信号通路相关蛋白表达。 结果 与对照组相比，DCM组大鼠左心室射血分数(EF)、左室短轴缩短率(FS)、舒张早期与晚期血流速度峰值比值(E/A)均显著降低，舒张末期左心室内径(LVEDd)增加，血清LDH、cTnI、CK-MB升高，心肌组织SOD、GSH降低，丙二醛、ROS和Fe2＋增加，转铁蛋白受体1(TFR1)、核受体共激活因子4(NCOA4)、LC3-II/LC3-I、Beclin-1、磷酸化AMPK及磷酸化ULK1表达水平升高，谷胱甘肽过氧化物酶4(GPX4)、溶质载体家族7成员11(SLC7A11)、磷酸化mTOR表达水平降低。与DCM组相比，各治疗组大鼠上述指标均得到显著改善。与TSPJ组相比，AMPK激动剂AICAR能够逆转TSPJ对DCM大鼠心肌细胞铁死亡及AMPK/mTOR/ULK1通路介导的铁自噬作用。 结论 TSPJ能够通过调控AMPK/mTOR/ULK1介导的铁自噬抑制DCM大鼠心肌细胞铁死亡，改善心肌损伤。 Objective To investigate the effect of total saponins of Panax japonicus(TSPJ) on ferroptosis of myocardial cells in diabetic cardiomyopathy(DCM) rats and underlying mechanism. Methods Experiment 1: SD rats were divided into control group, DCM group, low-dose TSPJ group, high-dose TSPJ group, and metformin(Met) group, with 10 rats in each group. Experiment 2: SD rats were divided into control group, DCM group, TSPJ group, adenosine monophosphate-activated protein kinase(AMPK) inhibitor Compound C group, and TSPJ+ AMPK agonist AICAR group, with 10 rats in each group. Except for the control group, all rats were intraperitoneally injected with streptozotocin to construct a DCM model. After 8 weeks of corresponding drug intervention, the body weight as well as glucose and lipid metabolism of rats in each experimental group were assessed, and the cardiac function indicators were detected with echocardiography. The levels of serum lactate dehydrogenase(LDH), cardiac troponin I(cTnI) and creatine kinase isoenzyme MB(CK-MB) were detected by ELISA technique. The pathological changes of myocardial tissue were observed using hematoxylin-eosin(HE) staining. The levels of dismutase(SOD), glutathione(GSH), malondialdehyde(MDA), reactive oxygen species(ROS) and Fe2+ in myocardial tissue were detected. Western blot was used to detect ferroptosis, ferritinophagy, and the AMPK/mammalian target of rapamycin/UNC-51-like kinase 1(mTOR/ULK1) signaling pathway related proteins expression in myocardial tissue. Results Compared with control group, left ventricular ejection fraction(EF), left ventricular short axis shortening rate(FS), peak blood velocity ratio(E/A) between early and late diastolic periods were significantly decreased in DCM group, left ventricular inner diameter(LVEDd) was increased, and the serum LDH, cTnI, CK-MB were increased, the levels of SOD, GSH were decreased, MDA, ROS, Fe2+ were increased in myocardial tissue, the expressions of TFR1, NCOA4 LC3-II/LC3-I, Beclin-1, phosphorylated AMPK and phosphorylated ULK1 were increased, the expressions of GPX4, SLC7A11 and phosphorylated mTOR were decreased. Compared with DCM group, the above indicators of rats were significantly improved in each treatment group. Compared with the TSPJ group, the AMPK agonist AICAR reversed the effects of TSPJ on ferroptosis and ferritinophagy mediated by the AMPK/mTOR/ULK1 pathway in DCM rat cardiomyocytes. Conclusion TSPJ can inhibit ferroptosis in DCM rat cardiomyocytes and improve myocardial injury by regulating AMPK/mTOR/ULK1 mediated ferritinophagy.

    糖尿病心肌病竹节参总皂苷铁死亡铁自噬AMPK/mTOR/ULK1通路

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    糖皮质激素过度敏感综合征病例报道一例并文献复习

    叶小珍许一新杨新怡王燕燕...
    64-67页
    查看更多>>摘要：本文报道1例具有典型库欣综合征临床表现而血皮质醇水平极低的糖皮质激素过度敏感综合征，经过糖皮质激素受体拮抗剂米非司酮治疗后患者的库欣症状明显缓解，血皮质醇水平恢复正常。本例报道旨在提高临床医师对糖皮质激素过度敏感综合征的认识。 This article reports a patient with typical Cushing syndrome′s manifestations and extremely low plasma cortisol level, indicating glucocorticoid hypersensitivity syndrome. After treatment with the glucocorticoid receptor antagonist mifepristone, the patient′s Cushing symptoms were significantly relieved, and cortisol levels returned to normal. The aim of this report is to enhance clinical awareness among physicians regarding glucocorticoid hypersensitivity syndrome.

    糖皮质激素过度敏感库欣综合征低皮质醇水平米非司酮

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