中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (35): 7537-7543.doi: 10.12307/2025.945

• 肌肉肌腱韧带组织构建 tissue construction of the muscle, tendon and ligament • 上一篇    下一篇

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

蔡之幸1，夏秋芳1，陈莉莉2，朱丹阳2，朱慧雯1，孙亚男1，梁文玉1，赵鹤倩1   

  1. 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


  • 收稿日期:2024-09-29 接受日期:2024-12-10 出版日期:2025-12-18 发布日期:2025-04-30
  • 通讯作者: 夏秋芳，硕士，主任医师，上海市第一康复医院中医康复科，上海市 200090
  • 作者简介:蔡之幸，女，1984年生，2011年上海中医药大学毕业，硕士，副主任医师，主要从事糖脂代谢紊乱性疾病的中医内科临床及科研工作。
  • 基金资助:
    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

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

Cai Zhixing1, Xia Qiufang1, Chen Lili2, Zhu Danyang2, Zhu Huiwen1, Sun Yanan1, Liang Wenyu1, Zhao Heqian1   

  1. 1Department of Traditional Chinese Medicine Rehabilitation, The First Rehabilitation Hospital of Shanghai, Shanghai 200090, China; 2Department of Traditional Chinese Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
  • Received:2024-09-29 Accepted:2024-12-10 Online:2025-12-18 Published:2025-04-30
  • Contact: Xia Qiufang, Master, Chief physician, Department of Traditional Chinese Medicine Rehabilitation, The First Rehabilitation Hospital of Shanghai, Shanghai 200090, China
  • About author:Cai Zhixing, Master, Associate chief physician, Department of Traditional Chinese Medicine Rehabilitation, The First Rehabilitation Hospital of Shanghai, Shanghai 200090, China
  • Supported by:

    National Natural Science Foundation of China (Youth Science Fund Project), No. 82205041 (to CZX); Special Project of Shanghai Yangpu District Health and Wellness System for Traditional Chinese Medicine, No. YPZHM202308 (to ZHW) 

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摘要：


文题释义：
柔肌顺膵饮：是中药复方，由黄芪、葛根、人参、黄连、生地、生白芍、徐长卿、延胡索组成，具有降糖、改善骨骼肌胰岛素抵抗的临床疗效。
AKT/GSK-3β通路：是骨骼肌代谢中的经典信号通路，胰岛素通过活化磷酸化AKT及其下游GSK-3β蛋白促进骨骼肌葡萄糖摄取。

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。
https://orcid.org/0000-0001-5689-9199(蔡之幸)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

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

Abstract:

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-GSK3β proteins 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, fasting insulin, and insulin resistance index were significantly reduced in the low- and high-dose Roujishuncuiyin groups and the positive control group (P < 0.05), the area under the curve of the oral glucose tolerance test was reduced (P < 0.05), the expression of p-AKT and p-GSK3β proteins in the tibialis anterior muscle was significantly elevated (P < 0.05), and mitochondrial damage in the tibialis anterior muscle was significantly ameliorated, with decreased lipid droplets in the interstitium. (3) The above indexes were better in the high-dose Roujishuncuiyin group than the low-dose Roujishuncuiyin group (P < 0.05), while there was no significant difference between the high-dose Roujishuncuiyin group and positive control group (P > 0.05). To conclude, by upregulating the protein levels of p-AKT and p-GSK3β in skeletal muscle tissue, the traditional Chinese medicine compound Roujishuncuiyin can improve structural disorders and mitochondrial morphology in skeletal muscle tissue, reduce insulin resistance in the skeletal muscle and regulate glucose homeostasis in the body.  


Key words: type 2 diabetes, Roujishuncuiyin, skeletal muscle, insulin resistance, signaling pathway, mitochondrial morphology, glucose homeostasis

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