和于泰辅助降糖片联合二甲双胍对糖尿病大鼠骨骼肌胰岛素抵抗的影响

1，2，孙文 2，宋紫临 2，郭璇 2，吴丽丽 2，秦灵灵 2，侯丹 3，张茁 3，田硕 3，李响 4，刘铜华 2

1.首都医科大学附属复兴医院，北京 100045；2.北京中医药大学，北京 100029；

3.陕西中医药大学，陕西 咸阳 712046；4.河北工程大学医学院，河北 邯郸 056000

摘要：目的 观察和于泰辅助降糖片联合二甲双胍对糖尿病大鼠骨骼肌胰岛素抵抗的影响，探讨其作用机制。方法 6～7周龄雄性ZDF（fa/fa）大鼠随机分为模型组、二甲双胍组、和于泰辅助降糖片组（降糖片组）、和于泰辅助降糖片联合二甲双胍组（联合组），另选ZDF（fa/+）大鼠为正常组，各给药组给予相应药物灌胃，连续 6周。检测体质量、空腹血糖（FBG）、三酰甘油、总胆固醇（TC）、游离脂肪酸（FFA）、血清胰岛素水平，计算胰岛素抵抗指数（HOMA-IR），并进行口服葡萄糖耐量实验（OGTT）；HE染色观察骨骼肌病理变化； RT-PCR 和 Western blot 分别检测骨骼肌相应基因和蛋白表达。结果 与二甲双胍组、降糖片组比较，联合组大鼠 TC、FFA、FBG 水平及 HOMA-IR 显著降低（P＜0.05，P＜0.01）；OGTT 各时间点血糖水平及曲线下面

积显著降低（P＜0.05，P＜0.01）；HE染色肌纤维排列整齐，细胞核无增多及内移，未见明显炎细胞浸润；骨骼肌胰岛素受体（InsR）、蛋白激酶B（Akt）、葡萄糖转运蛋白 4（Glut4）mRNA 表达显著升高（P＜0.05，P＜

0.01）；骨骼肌磷酸化 InsR、磷酸化 Akt、Glut4 蛋白表达显著升高（P＜0.05，P＜0.01）。结论 和于泰辅助降糖片联合二甲双胍能够改善2型糖尿病大鼠胰岛素抵抗，效果优于单独应用。

关键词：和于泰辅助降糖片；二甲双胍；联合应用；PI3K/Akt信号通路；大鼠

DOI：10.3969/j.issn.1005-5304.2017.11.010

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304(2017)11-0039-05

Effects of Heyutai Fuzhu Jiangtang Tablets Combined with Metformin on Insulin Resistance in Skeletal Muscle of Diabetic Rats

XU Guang-yuan1,2, SUN Wen2, SONG Zi-lin2, GUO Xuan2, WU Li-li2, QIN Ling-ling2, HOU Dan3, ZHANG Zhuo3, TIAN Shuo3, LI Xiang4, LIU Tong-hua2 (1. Fuxing Hospital of Capital Medical University, Beijing 100045, China; 2. Beijing University of Chinese Medicine, Beijing 100029, China; 3. Shaanxi University of Chinese Medicine, Xianyang 712046, China; 4. Medical College of Hebei University of Engineering, Handan 056000, China)

Abstract: Objective To observe effects of Heyutai Fuzhu Jiangtang Tablets combined with metformin in insulin resistance (IR); To discuss its mechanism of action. Methods 6–7 week old male ZDF (fa/fa) rats were randomly divided into model group, metformin group, Heyutai Fuzhu Jiangtang Tablets group (Jiangtang Tablets group), and metformin combined with Heyutai Fuzhu Jiangtang Tablets group. ZDF (fa/+) rats were chosen as normal group. Each medication group was given relevant medicine for gavage for 6 weeks. Body weight, FBG, TG, TC, FFA, FINS, HOMA-IR, OGTT and HE staining were tested. HE staining was used to observe the pathological changes of skeletal muscle. RT-PCR and Western blot were used to detect skeletal muscle corresponding gene and protein expression. Results Compared with Jiangtang Tablets group and metformin group, TC, FFA, FBG, and HOMA-IR in metformin combined with Heyutai Fuzhu Jiangtang Tablets group decreased significantly (P<0.05, P<0.01). Blood glucose level and AUC significantly decreased at each time point in OGTT. HE staining of skeletal muscle fibers arranged in order; nucleus increased and internal movement was not significant, without obvious infiltration of inflammatory cells. Expressions of skeletal muscle InsR, Akt, and Glut4 mRNA expression increased (P<0.05, P<0.01). Expressions of skeletal muscle p-InsR, p-Akt, and

基金项目：北京市教育委员会高校重大成果转化项目（2014年）

通讯作者：刘铜华，E-mail：thliu@vip.163.com