糖胰敏对实验性胰岛素抵抗糖尿病大鼠脂毒性和胰岛素抵抗的影响

Effects of Tangyimin on Lipotoxicity and Insulin Resistance in Experimental T2DM Rats with Insulin Resistance

目的:探讨糖胰敏对实验性胰岛素抵抗糖尿病模型大鼠脂毒性和胰岛素抵抗的改善作用,明确糖胰敏治疗2型糖尿病(T2DM)的机理。方法:采用高糖高脂饲料喂养联合低剂量链脲佐菌素(STZ)腹腔注射建立实验性胰岛素抵抗(IR)糖尿病大鼠模型。实验分为正常对照组、模型对照组、达美康对照组、糖胰敏高、中、低剂量组。治疗前及治疗1周后开始动态监测各组大鼠体质量及空腹血糖(FBG)。治疗4周后,血糖仪检测空腹血糖,全自动生化仪检测血脂,放射免疫检测法测定血清胰岛素(FINS)。计算体重指数(BMI)、胰岛素抵抗指数(IRI)、胰岛素敏感指数(ISI)、胰岛素分泌指数(IS),HE染色观察胰腺组织病理形态学变化。结果:T2DM模型组大鼠体质量和BMI较正常对照组显著增高(P<0.01,P<0.05);治疗4周后,糖胰敏中、高剂量组及达美康组大鼠体质量和BMI较治疗前明显下降(P<0.05)。与正常对照组比较,模型组大鼠血糖、血清FINS、TG、TC、LDL,IRI明显升高(P<0.05),ISI、IS、HDL明显降低(P<0.05);糖胰敏治疗2周后大鼠血糖开始下降,治疗4周后,糖胰敏中、高剂量组以及达美康组大鼠空腹血糖、TC、TG、LDL-C、IRI均明显降低(P<0.05),而HDL-C、ISI和IS明显升高(P<0.05);胰腺组织病理形态学观察结果显示糖胰敏组胰腺形态结构较模型组清晰完整,胰岛数量及胰岛内细胞数量较模型组明显增多,胰岛形态结构明显较模型组清晰完整,且糖胰敏高剂量组对胰岛病理形态学的改善作用最显著。结论:中药复方糖胰敏可通过调节糖脂代谢,降低脂毒性,改善胰岛β细胞功能,增强组织对胰岛素的敏感性,从而有效降低实验性胰岛素抵抗糖尿病大鼠的血糖。

Objective：To investigate the improvement of Tangyimin（TYM） on lipotoxicity and insulin resistance（IR） in experimental type 2 diabetes mellitus（T2DM） rats with IR,and indentify the mechanism of TYM for T2DM treatment.Methods：Experimental T2DM model rats with IR were established by feeding with high calorie diet combined with intraperitoneal injection of low dose STZ.The experiment was designed for 6 groups：normal control group,T2DM model group,low,middle,high dose TYM groups and diamicron group.The body mass and fasting blood glucose （FBG） level were periodically detected dynamically at prior treatment and after treatment for 1 week.After treatment for 4 weeks,the FBG level was measured using glucose meter,the levels of blood fats were measured by using automatic biochemical analyzer,the fasting serum insulin（FINS） was detected by radioimmunoassay,the body mass index（BMI）,insulin resistance index（IRI）,insulin sensitivity index（ISI） and insulin secretion index（IS） were calculated.The pathomorphology change of pancreatic tissue were observed by hematoxylin-eosin（HE） stain.Results：The body,mass and BMI of T2DM model group were significantly higher than those of normal control group（P ＜0.01,P ＜0.05）,the rats＇body mass and BMI at post-treatment were lower obviously than those at prior-treatment in TYM middle-dose group,TYM high-dose group and Diamicron group （P ＜ 0.05）.Compared with the normal control group,the serum FBG,FINS,TC,TG,LDL -C levels and IRI in the model group were all increased significantly （P ＜ 0.05）,meanwhile,the serum HDL -C level,ISI and IS were all markedly decreased （P ＜ 0.05）.The FBG level was began to descend after treatment for 2 weeks,after treated for 4 weeks,the levels of FBG,TC,TG,LDL-C and IRI were decreased notably （P ＜ 0.05）,otherwise,the HDL-C level,ISI and IS were significantly increased （P ＜ 0.05）,the results of pancreatic tissue pathomorphology observation showed that the morphological structures of pancreas in TYM treatment groups were clearer and more integrated than the model group,the amount of islets and islet cells was significantly increased to compare with the model group.The islets＇ integrity in TYM treatment groups was significantly clearer than the model group,and the improvement in TYM high-dose group was specially notable.Conclusions：TYM could regulate the glycolipids metabolism,reduce lipotoxicity,improve islet beta cells＇ function and enhance tissues＇ sensitivity to insulin,thus effectively reduce the FBG level in experimental IR diabetes rats,meanwhile,play the role of improving the lipid disorders and depressing IR.