大黄黄连泻心汤对2型糖尿病大鼠骨骼肌中AMPKα、PGC-1α、GLUT4表达的影响  

Effect of Dahuang Huanglian Xiexin Decoction on the expression of AMPKα, PGC-1α and GLUT4 in skeletal muscle of type 2 diabetic rats

作　　者：郝建华 包毅敏[2] 包芸[3] 鹿伟[3] 张超伟 郝艺杰 HAO Jianhua;BAO Yimin;BAO Yun;LU Wei;ZHANG Chaowei;HAO Yijie(School of Traditional Chinese Medicine,Inner Mongolia Medical University,Inner Mongolia Autonomous Region,Hohhot010030,China;Department of Orthopaedics,the Affiliated Hospital of Inner Mongolia Medical University,Inner Mongolia Autonomous Region,Hohhot010050,China;Department of Traditional Chinese Medicine,the Affiliated Hospital of Inner Mongolia Medical University,Inner Mongolia Autonomous Region,Hohhot010050,China)

机构地区：[1]内蒙古医科大学中医学院,内蒙古呼和浩特010030 [2]内蒙古医科大学附属医院骨科,内蒙古呼和浩特010050 [3]内蒙古医科大学附属医院中医科,内蒙古呼和浩特010050

出　　处：《中国医药导报》2019年第33期13-18,共6页China Medical Herald

基　　金：内蒙古自治区自然科学基金项目(2016MS0827)

摘　　要：目的探讨大黄黄连泻心汤对2型糖尿病大鼠骨骼肌中腺苷酸活化蛋白激酶α(AMPKα)、过氧化物酶体增殖活化受体γ共激活因子-1α(PGC-1α)、葡萄糖转运蛋白4(GLUT4)表达的影响。方法40只SPF级健康雄性Wister大鼠按照随机数字表法分为空白对照组10只和造模组30只。造模组采用高糖高脂饲料联合小剂量链脲佐菌素法制备2型糖尿病大鼠模型,造模成功后按照随机数字表法分为模型组、中药组、二甲双胍组,每组各10只。中药组按照1 g/(100 g·d)予以大黄黄连泻心汤灌胃,二甲双胍组按照18 mg/(100 g·d)灌胃给药,空白对照组和模型组分别予以等量生理盐水。4周后检测大鼠空腹血糖(FPG)、胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C),光镜下观察胰腺组织病理形态学改变,RT-PCR法检测大鼠骨骼肌中AMPKα、PGC-1α、GLUT4的mRNA表达,Western blot法检测AMPKα、磷酸化的腺苷酸活化蛋白激酶α(P-AMPKα)、PGC-1α、GLUT4蛋白表达。结果造模后,与空白对照组比较,造模组FPG显著升高(P<0.01),造模成功。以大黄黄连泻心汤灌胃4周后,与模型组比较,中药组FPG、TC、TG、LDL-C明显降低(P<0.01或P<0.05),骨骼肌中AMPKα、PGC-1α、GLUT4表达量增高(P<0.01或P<0.05),光镜下观察胰岛结构较完整,胰岛β细胞变性程度较轻,空泡细胞数量减少。结论大黄黄连泻心汤的降糖作用机制与AMPK信号通路相关,通过激活AMPKα,上调PGC-1α、GLUT4的表达,来调节糖脂代谢。Objective To observe the effect of Dahuang Huanglian Xiexin Decoction on AMP-acticated protein kinaseα(AMPKα),peroxisome proliferator activated receptor-γcoactivator-1α(PGC-1α),and glucose tRNAsporter 4(GLUT4)expression in skeletal muscle of type 2 diabetic rats.Methods According to the random number table method,40 healthy SPF male Wister rats were divided into the blank control group with 10 rats and the building model group with 30 rats.The building model group was prepared by using high-sugar and high-fat diet combined with a small dose streptozotocin to prepare the rat model of type 2 diabetes mellitus.After successful modeling,the building model group was divided into the model group,the traditional Chinese medicine group and the Metformin group according to the random number table,with 10 rats in each group.The traditional Chinese medicine group was given Dahuang Huanglian Xiexin Decoction with a dose of 1 g/(100 g·d).The Metformin group was given Metformin by gavage with a dose of 18 mg/(100 g·d).The blank control group and model group were given the same amount of saline. After 4 weeks, fasting blood glucose (FPG), cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were detected in the rats, and pathomorphological changes of pancreatic tissue were observed under optical microscope. RT-PCR was used to detect mRNA expressions of AMPKα, PGC-1α, GLUT4 in skeletal muscle of rats. The expressions of AMPKα, phosphorylated AMPKα (P-AMPKα), PGC-1α and GLUT4 were detected by Western blot. After modeling, compared with the blank control group, FPG in the building model group was significantly increased (P < 0.01), which means models were induced successfully. With gavaging Dahuang Huanglian Xiexin Decoction for 4 weeks, compared with the model group, FPG, TC, TG, LDL-C of the traditional Chinese medicine group significantly decreased (P < 0.01 or P < 0.05), and the expressions of AMPKα, PGC-1α, GLUT4 obviously increased in skeletal muscle (P < 0.01 or P < 0.05). Under

关 键 词：大黄黄连泻心汤 糖尿病大鼠 腺苷酸活化蛋白激酶α 过氧化物酶体增殖活化受体γ共激活因子-1α 葡萄糖转运蛋白4 

分 类 号：R285.5[医药卫生—中药学]