葛根芩连汤对肥胖2型糖尿病前期胰岛素抵抗伴缺氧大鼠肾组织HIF-2α、EPO及GILUT4表达的影响  

Gegen Qinlian Decoction(葛根芩连汤)Regulates Expression of HIF-2α,EPO,and GILUT4 in Renal Tissue of Obese Rat Model of Insulin Resistance and Hypoxia Predisposing to Type 2 Diabetes Mellitus

作　　者：刘海云[1] 占诗梦 彭淑红[2,3,4] 方永青 许清松 高金青 陈凌昊 张启云 姜丽[2,3,4] 李冰涛 曾治君[2,3,4] 徐国良 LIU Haiyun;ZHAN Shimeng;PENG Shuhong;FANG Yongqing;XU Qingsong;GAO Jinqing;CHEN Linghao;ZHANG Qiyun;JIANG Li;LI Bingtao;ZENG Zhijun;XU Guoliang(School of Chinese Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004;Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory,Jiangxi University of Chinese Medicine,Nanchang 330004;Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Etiopathogenisis,Nanchang 330004;Key Laboratory of Pharmacology of Traditional Chinese Medicine,Nanchang 330004)

机构地区：[1]江西中医药大学中医学院,南昌330004 [2]江西中医药大学中医基础理论分化发展研究中心,南昌330004 [3]江西省中医病因生物学重点实验室,南昌330004 [4]江西省中药药理重点实验室,南昌330004

出　　处：《中药药理与临床》2024年第1期3-8,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(82060826);江西省中医药管理局科技计划重点项目(2022Z027);江西中医药大学研究生创新专项项目(JZYC21B02、JZYC23S10);江西中医药大学大学生创新创业训练项目(X202310412248、202211417);江西中医药大学校级科技创新团队发展计划项目(CXTD22007)。

摘　　要：目的:研究葛根芩连汤对肥胖2型糖尿病前期胰岛素抵抗伴缺氧大鼠肾组织缺氧诱导因子-2α(HIF-2α)、促红细胞生成素(EPO)及葡萄糖转运蛋白4(GLUT4)表达的影响。方法:SD大鼠72只随机分为正常对照组、高脂造模组。高脂造模组以高脂饲料喂养13 w,建立肥胖2型糖尿病前期胰岛素抵抗伴缺氧模型。将造模成功大鼠随机分为模型对照组、罗格列酮5 mg/kg组、葛根芩连汤1.65、14.85 g/kg组,连续给药16 w,1次/d,记录体质量、体长、lee’s指数;放射免疫法检测空腹胰岛素水平(FINS);全自动生化分析仪检测空腹血糖(FBG)、肌酐(Scr)、尿素氮(BUN)、尿酸(UA)含量;ELISA法检测HIF-2α、EPO含量;HE染色观察肾组织形态改变;实时荧光定量PCR和Western blot法检测肾脏组织Hif2a、Epo、Glut4 mRNA及蛋白表达。结果:与正常对照组比较,模型对照组大鼠体质量、lee’s指数显著增加(P<0.01),空腹血糖(FBG)、胰岛素水平(FINS)显著升高、胰岛素抵抗指数(HOMAIR)显著增加(P<0.01),肾脏组织Hif2a、Epo mRNA及蛋白表达明显上调、Glut4 mRNA及蛋白表达明显下调(P<0.05或P<0.01);与模型对照组比较,葛根芩连汤1.65、14.85 g/kg组大鼠体质量、lee’s指数明显降低(P<0.05),FBG、FINS、HOMA-IR水平明显降低(P<0.05或P<0.01),肾脏组织Hif2a、Epo mRNA及蛋白表达明显下调、Glut4 mRNA及蛋白表达明显上调(P<0.05或P<0.01)。结论:葛根芩连汤可降低肥胖2型糖尿病前期胰岛素抵抗伴缺氧模型大鼠HIF-2α、EPO的表达,上调GLUT4表达,明显改善模型大鼠胰岛素抵抗及肾脏缺氧,延缓糖尿病肾病的发生发展。Objective:To investigate the effects of Gegen Qinlian Decoction(葛根芩连汤,GQD)on the expression of hypoxia-inducing factor-2α(HIF-2α),erythropoietin(EPO),and glucose transporter 4(GLUT4)in the renal tissue of the rat model of insulin resistance and hypoxia.Methods:Seventy-two SD rats were randomized into a normal control group and a modeling group.The rat model of insulin resistance and hypoxia was established by a high-fat diet for 13 weeks.The successfully modeled rats were randomized into model control,rosiglitazone(5 mg/kg),and GQD(1.65 g/kg and 14.85 g/kg)groups.Rats were administrated with corresponding drugs once a day for 16 consecutive weeks.The body mass,body length,and Lee’s index were recorded.The radioimmunoassay was employed to measure the level of fasting insulin(FINS),an automatic biochemical analyzer was used to measure the levels of fasting blood glucose(FBG),serum creatinine(Scr),urea nitrogen(BUN),and uric acid(UA).HIF-2αand EPO were detected by enzyme-linked immunosorbent assay(ELISA).The morphological changes of the renal tissue were observed by hematoxylin-eosin(HE)staining.The mRNA and protein levels of Hif-2α,Epo,and Glut4 were determined by real-time quantitative PCR and Western blotting,respectively.Results:Compared with the normal control group,the model control group showed increased body weight,Lee’s index,and homeostasis model assessment-insulin resistance(HOMA-IR)and elevated levels of FBG and FINS(P<0.01).In addition,the model group presented up-regulated mRNA and protein levels of Hif-2αand Epo and down-regulated mRNA and protein levels of Glut4 in the renal tissue(P<0.05,P<0.01).Compared with the model control group,1.65 g/kg and 14.85 g/kg GQD decreased the body weight,Lee’s index,and HOMA-IR,lowered the levels of FBG and FINS,down-regulated the mRNA and protein levels of Hif-2αand Epo,and up-regulated the mRNA and protein levels of GLUT4 in the renal tissue(P<0.05 or P<0.01).Conclusion:GQD can down-regulate the expression of HIF-2αand EPO and up-regulated th

关 键 词：葛根芩连汤 2型糖尿病 胰岛素抵抗 缺氧 缺氧诱导因子2α 促红细胞生成素 葡糖糖转运蛋白4 

分 类 号：R285.5[医药卫生—中药学]