辛开苦降方对初发2型糖尿病KKAy小鼠胰岛素敏感性及糖脂代谢的影响

目的:观察辛开苦降方干预初发2型糖尿病(T2DM)KKAy小鼠胰岛素敏感性及糖脂代谢的影响。方法:10周龄雄性初发T2DM KKAy小鼠40只按血糖值随机分为4组:模型组、罗格列酮组、辛开苦降低剂量组、辛开苦降高剂量组。正常对照组选10周龄雄性C57BL/6J小鼠10只。正常组及模型组给予0.5%羧甲基纤维素钠溶液(CMC)灌胃。各组连续灌胃给药四周后取材,测定其空腹血糖(Fasting Plasma glucose,FPG)、血清胰岛素(Fasting Insulin,FINS)、血脂,肝糖原、肝脂质含量。显微镜下观察肝脏组织形态。结果:给药四周后,与正常组相比,模型组胰岛素敏感指数(Insulin Sensitivity Index,ISI)明显降低(P0.01),FPG、FINS、总胆固醇(Total Cholesterol,TC)、三酰甘油(Triglyceride,TG)、游离脂肪酸(Free Fatty Acid,FFA)、肝脏TC、肝脏TG均明显升高(P0.01),肝糖原含量降低(P0.01)。与模型组相比,罗格列酮组ISI好转(P0.01),FPG、FINS、TC、TG、FFA、TG明显降低(P0.01,P0.05),肝糖原含量明显增加(P0.01)。辛开苦降低剂量组及其高剂量组2组FINS、ISI、肝糖原含量均高于模型组(P0.05,P0.01),TG水平低于模型组(P0.05,P0.01);辛开苦降高剂量还能显著降低FPG、TC水平、FFA水平(P0.05,P0.01)。辛开苦降低剂量组还可显著降低肝脏TG水平(P0.05)。肝脏病理显示:正常组小鼠肝脏结构正常,而模型组小鼠肝脏脂肪变性明显。罗格列酮组小鼠肝脏脂肪变性较模型组有所减轻。辛开苦降低剂量组和辛开苦降高剂量组小鼠肝脂肪变性较模型组有明显改善。结论:辛开苦降方可增加KKAy T2DM小鼠胰岛素敏感性,减轻肝胰岛素抵抗,肝糖原合成增加,从而改善血糖水平,并能降低血及肝脏脂质水平,减轻肝脏脂肪变性,有效保护肝脏组织形态结构。

Effects of Xinkaikujiang Formula on Insulin Sensitivity and Glucolipid Metabolism in KKAy Mice with Incipient Type 2 Diabetes Mellitus

Objective：To observe the intervention effects of XinkaiKujiang formula on insulin sensitivity and glucolipid metabolism in KKAy mice with incipient type 2 diabetes mellitus （T2DM）.Methods：KKAy mice with type 2 diabetes mellitus were randomly assigned into the following four groups according to blood glucose levels：the model group,Rosiglitazone group,XinKaiKuJiang-low dose group （XK-L）,XinKaiKuJiang-high dose（XK-H）group.Ten male C57BL/6J mice （10 weeks old）served as a non-diabetic control group. The mice in the control and model groups were intragastrically administered with 0.5% sodium carboxymethyl cellulose solution.Blood and tissue samples were collected after 4 weeks of treatment.Contents of fasting plasma glucose （FPG）,fasting insulin （FINS）,blood lipid,hepatic glycogen and liver lipid were detected,and pathological morphology in liver was observed under the microscope.Results：After 4 weeks of treatment,compared with the normal group,the insulin sensitivity index （ISI）in the model group was apparently de-creased （P〈0.01）.The levels of FPG,FINS,total cholesterol （TC）,triglyceride （TG）,free fatty acid （FFA）,liver total cholesterol and liver triglycerides were significantly increased （P〈0.01）.The content of hepatic glycogen was decreased （P〈0.01）.Compared with the model group,ISI in the Rosiglitazone group was improved（P〈0.01）.FPG,FINS,TC,TG,FFA,and liver total cholesterol were significantly decreased （P〈0.01,P〈0.05）.The content of hepatic glycogen was significantly increased （P〈0.01）.FINS,ISI,con-tent of hepatic glycogen in the XK-L group and XK-H group were all higher than those in the model group （P〈0.05,P〈0.01）,and the level of TG was lower than that in the model group （P〈0.05,P〈0.01）.The levels of FPG,TC and FFA could also be decreased in XK-H group （P〈0.05,P〈0.01）.The XK-L group also could significantly decrease the liver triglyceride level （P〈0.05）.According to hepatic pathology,the liver structures of mice in the normal group were normal,while the livers of mice in the model group had marked＆nbsp;fatty degeneration.Compared with model group,there was a lighter fatty degeneration of livers in Rosiglitazone group,and fatty degenera-tion of livers was significantly improved in the XK-L group and XK-H group.Conclusion：The XinkaiKujiang formula could enhance the insulin sensitivity in KKAy mice with T2DM,reduce hepatic insulin resistance,and increase the content of hepatic glycogen,further im-prove blood sugar levels.It also could lower the lipid level in blood and liver,reduce fatty degeneration of livers,and protect the morpho-logical structure of liver tissues effectively.