柔肌顺膵饮改善2型糖尿病小鼠骨骼肌胰岛素抵抗的作用  

Effect of Roujishuncuiyin on the improvement of skeletal muscle insulin resistance in a mouse model of type 2 diabetes mellitus

作　　者：蔡之幸 夏秋芳 陈莉莉 朱丹阳 朱慧雯 孙亚男 梁文玉 赵鹤倩 Cai Zhixing;Xia Qiufang;Chen Lili;Zhu Danyang;Zhu Huiwen;Sun Yanan;Liang Wenyu;Zhao Heqian(Department of Traditional Chinese Medicine Rehabilitation,The First Rehabilitation Hospital of Shanghai,Shanghai 200090,China;Department of Traditional Chinese Medicine,Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200336,China)

机构地区：[1]上海市第一康复医院中医康复科,上海市200090 [2]上海交通大学医学院附属同仁医院中医科,上海市200336

出　　处：《中国组织工程研究》2025年第35期7537-7543,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金青年科学基金项目(82205041),项目负责人:蔡之幸;上海市杨浦区卫生健康系统中医药专项课题(YPZHM202308),项目负责人:朱慧雯。

摘　　要：背景:骨骼肌胰岛素抵抗是2型糖尿病的关键病理环节,中药复方柔肌顺膵饮可有效改善骨骼肌胰岛素抵抗,但作用机制尚未明确。目的:探讨柔肌顺膵饮对2型糖尿病小鼠骨骼肌胰岛素抵抗的作用机制。方法:将40只2型糖尿病db/db小鼠随机分为模型组10只、柔肌顺膵饮低剂量组10只,柔肌顺膵饮高剂量组10只、阳性对照组10只,取10只db/dm小鼠为空白对照组。柔肌顺膵饮低、高剂量组和阳性对照组分别以157.5,630 mg/g柔肌顺膵饮和200 mg/g二甲双胍水溶液灌胃,1次/d,模型组和空白对照组给予等剂量生理盐水灌胃。给药12周后检测各组小鼠空腹血糖;行口服葡萄糖耐量实验并计算血糖曲线下面积;ELISA检测血清胰岛素水平并计算胰岛素抵抗指数;透射电镜观察胫骨前肌组织线粒体超微结构;Western blot检测胫骨前肌AKT、GSK-3β蛋白表达量及磷酸化水平。结果与结论:①与空白对照组相比,模型组空腹血糖、空腹胰岛素和胰岛素抵抗指数显著升高(P<0.05),口服葡萄糖耐量实验曲线下面积显著增加(P<0.05),胫骨前肌p-AKT、p-GSK3β蛋白表达量显著降低(P<0.05),胫骨前肌有大量线粒体损伤,间质存在大量脂滴;②与模型组相比,柔肌顺膵饮低、高剂量组及阳性对照组空腹血糖、空腹胰岛素和胰岛素抵抗指数显著降低(P<0.05),口服葡萄糖耐量实验曲线下面积减少(P<0.05),胫骨前肌p-AKT、p-GSK3β蛋白表达量显著升高(P<0.05),胫骨前肌线粒体损伤显著改善,间质脂滴减少;③柔肌顺膵饮高剂量组上述指标均优于柔肌顺膵饮低剂量组(P<0.05),柔肌顺膵饮高剂量组上述指标与阳性对照组无显著差异(P>0.05);④结果表明,中药复方柔肌顺膵饮可能通过上调骨骼肌组织中AKT、GSK-3β蛋白的磷酸化水平,从而改善骨骼肌组织结构紊乱和线粒体形态异常,减轻骨骼肌胰岛素抵抗,调节机体葡萄糖稳态。BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.The traditional Chinese medicine compound Roujishuncuiyin can effectively improve skeletal muscle insulin resistance,but its mechanism has not been clarified.OBJECTIVE:To explore the mechanism of Roujishuncuiyin on skeletal muscle insulin resistance in type 2 diabetes mice.METHODS:Forty db/db mice with type 2 diabetes mellitus were randomized into a model group,a low-dose Roujishuncuiyin group,a high-dose Roujishuncuiyin group,and a positive drug group,with 10 mice in each group.The latter three administration groups were given 157.5 mg/g and 630 mg/g Roujishuncuiyin and 200 mg/g metformin hydrochloride aqueous solution by gavage once a day,respectively.In addition,10 db/dm mice were selected as the blank control group.Mice in the model and blank control groups were given the same dose of 0.9%NaCl solution by gavage.After 12 weeks of intervention,fasting blood glucose was measured in each group of mice,and oral glucose tolerance test was performed to calculate the area under the blood glucose curve.ELISA was used to detect serum insulin level and calculate the resistance index.Mitochondrial structure of skeletal muscle tissue was observed under transmission electron microscopy.Western blot was used to detect the expression levels and phosphorylation levels of protein kinase B(AKT)and glycogen synthase kinase 3β(GSK-3β)proteins in skeletal muscle.RESULTS AND CONCLUSION:(1)Compared with the blank control group,fasting blood glucose,fasting insulin and insulin resistance index were significantly higher in the model group(P<0.05),the area under the curve of the oral glucose tolerance test was significantly increased(P<0.05),the expression of p-AKT and p-GSK3βproteins in tibialis anterior muscle was significantly decreased(P<0.05),and there was a large amount of mitochondrial damage in tibialis anterior muscle and a large number of lipid droplets in the interstitium.(2)Compared with the model group,fasting blood glucose,fa

关 键 词：2型糖尿病 柔肌顺膵饮 骨骼肌 胰岛素抵抗 信号通路 线粒体形态 葡萄糖稳态 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R285.5