1型11β-羟基类固醇脱氢酶在实验性2型糖尿病大鼠模型骨骼肌中的表达及意义

Expression of 11β-hydroxysteroid dehydrogenase 1 in skeletal muscle in rats with type 2 diabetes

目的:探讨糖皮质激素代谢酶1型11β-羟基类固醇脱氢酶(11β-HSD1)及其受体(GR)在2型糖尿病大鼠骨骼肌蛋白表达的改变及意义。方法:Wistar大鼠随机分为对照组及模型组。高脂饮食联合链脲佐菌素(STZ)(30mg·kg-1)2次腹腔注射建立糖尿病模型。造模8周后大鼠剪尾取血,氧化酶法检测空腹血糖水平;放射免疫法检测空腹胰岛素水平,并计算胰岛素相关指数。Western blotting检测11β-HSD1和GR的蛋白表达。结果:与正常对照组比较,模型组的胰岛素分泌指数(IS)、胰岛素敏感指数(ISI)及HOMAβ细胞分泌指数(HβCI)明显下降(P<0.05),而胰岛素抵抗指数(IRI)显著升高(P<0.05),表明模型组有明显的胰岛素抵抗,合并有胰岛素分泌不足。与对照组比较,模型组骨骼肌组织中11β-HSD1及GR的蛋白表达增加(P<0.05)。结论:高脂饮食联合小剂量STZ注射建立的实验性糖尿病模型具有高血糖、胰岛素分泌功能受损及胰岛素抵抗特征;糖尿病模型骨骼肌组织中11β-HSD1及GR的蛋白表达显著增加。

Objective To investigate the changes of the expression of corticosteroids metabolic enzymes 11β-hydroxysteroid dehydrogenase 1（11β-HSD1）and glucocorticoid receptor（GR）in skeletal muscle in type 2 diabetic rat model and significance.Methods The Wistar rats were devided into control and type 2diabetic model groups.The models were built with a combination of high fat diet （HFD）and multiple low dose of STZ （30mg·kg-1,twice）injection.8weeks later,the blood of rats were colleted by cutting their tail,the blood glucose was tested with the method of oxidizing enzyme.According to the serologic test and the relevant index of insulin,the damage of islet and the secretion of insulin were determined.The protein expressions of corticosteroids metabolic enzymes 11β-HSD1 and GR in skeletal muscle were examined by Western blotting analysis. Results Compared with control group,the insulin secretion （IS）,insulin sensitivity index （ISI）andsecretion index of HOMAβcell（HβCI）were decreased significantly（P〈0.05）,while the insulin resistance index（IRI）was increased significantly（P〈0.05）.The protein expressions of 11β-HSD1and GR in model group were higher than those in control group （P〈0.05）.Conclusion The type 2diabetic model built with a combination of HFD and multiple low dose of STZ injection has the characteristics of high blood glucose,damage of IS function and insulin resistance.In the type 2diabeic models the protein expressions of 11β-HSD1and GR are significantly increased.