摘要
目的:通过糖皮质激素联合高脂喂养建立2型糖尿病(T2DM)大鼠模型,观察黄芪散及其拆方对T2DM大鼠胰岛素抵抗及肝组织11β-羟基类固醇脱氢酶1(11β-HSD1),磷酸烯醇式丙酮酸羧激酶(PEPCK)mRNA与蛋白表达的影响。方法:SD大鼠适应性饲养1周后,将大鼠随机分为正常组,糖皮质激素组(GC),高脂饮食组(HFD),高脂+糖皮质激素复合模型组(HFD+GC),罗格列酮组,黄芪散处方1组(HQS-1,2.91 g·kg^(-1)),黄芪散处方2组(HQS-2,3.85 g·kg^(-1))和黄芪散原方组(HQS,2.96 g·kg^(-1)),每组8只。正常组和GC组大鼠喂以基础饲料,其他各组喂以高脂饲料。同时除正常组和HFD组给予等体积的生理盐水外,其他各组大鼠灌胃醋酸泼尼松龙(3.5 mg·kg^(-1),每天1次),并于1 h后灌胃相应受试药物。于给药10周后,测定各组大鼠空腹血糖(FBG)及胰岛素(FINS)含量,并计算胰岛素敏感指数(ISI);苏木素-伊红(HE)染色法观察各组大鼠肝脏病理变化;实时荧光定量-聚合酶链式反应(Real-time PCR)和蛋白质免疫印迹(Western blot)法检测肝组织中11β-HSD1,PEPCK mRNA和蛋白表达水平。结果:与正常组比较,HFD+GC复合模型组大鼠表现为高血糖、高胰岛素血症,肝细胞变性,肝11β-HSD1,PEPCK表达显著性升高(P<0.01),病理学检测发现大鼠肝脏组织的病变较为明显。与HFD+GC复合模型组比较,各受试药物均不同程度地降低糖尿病大鼠FBG,FINS水平,提高ISI水平(P<0.05,P<0.01),对肝组织病理学形态也有不同程度的改善。比较HQS-1,HQS-2和罗格列酮的作用幅度,黄芪散原方对FINS水平及肝组织病理形态的改善更明显。HQS及其拆方均可不同程度地降低肝11β-HSD1,PEPCK mRNA和蛋白水平(P<0.05,P<0.01),且黄芪散原方组对11β-HSD1的降低幅度优于其他各组。结论:黄芪散具有提高胰岛素敏感性、改善肝脏病理的作用,其发挥防治糖尿病及改善胰岛素抵抗的作用机制可能与降低11β-HSD1水平有关。
Objective：To observe the effect of Huangqisan and its disassembled recipes on insulin resistance and mRNA and protein expression levels of 11 beta-hydroxysteroid dehydrogenase typem 1（11β-HSD1）,phosphoenolpyruvate carboxykinase（PEPCK） in type 2 diabetic rats induced by glucocorticoid and high fat diet.Method：The study was performed after the rats received adaptive feeding for 1 week.Rats were randomly divided into normal control group（CD）,glucocorticoid group（GC）,high fat diet group（HFD） and combined model group（HFD ＋ GC）,rosiglitazone group（Ros）,Huangqisan prescription 1 group（HQS-1,2.91 g·kg-1）,Huangqisan prescription 2 group（HQS-2,3.85 g·kg-1）,and Huangqisan original prescription group（HQS,2.96 g·kg-1）,8 rats in each group.The rats in CD and GC groups were fed with basic diet,and other groups were fed with high-fat diet.The rats in CD and HFD groups were given with the same volume of normal saline,and the rats in other groups were given with prednisolone acetate（3.5 mg·kg-1） by intragasic administration once a day,and then the corresponding testing drugs were given one hour later by intragasic administration.After intervention by drugs for 10 weeks,fasting blood glucose（FBG）,insulin levels and insulin sensitivity index（ISI） of all rats were measured.The liver pathological changes were observed by HE staining;and the mRNA and protein expression levels of 11β-HSD1 and PEPCK in liver issues were detected by Real-time PCR and Western blot methods.Result：As compared with CD group,the rats in HFD ＋ GC model group showed hyperglycemia,hyperinsulinemia,hepatocyte degeneration,and increased expression of 11β-HSD1 and PEPCK（P〈0.01）,and pathological examination showed that the pathological changes of liver tissues were obvious.As compared with HFD ＋ GC model group,each treatment group could decrease FPG and insulin levels,increase ISI to some degree,and also improve pathological morphology to some degree.The effect of HQS original prescription o
作者
李艳
高英
高颖
王春怡
郝梦娇
李卫民
LI Yan GAO Ying(School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2017年第15期136-142,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81373775
81503375)
关键词
黄芪散
2型糖尿病
胰岛素抵抗
11Β-羟基类固醇脱氢酶1
Huangqisan
type 2 diabetic
insulin resistance
11 beta-hydroxysteroid dehydrogenase typem 1（11β-HSD1）
