大黄黄连泻心汤改善2型糖尿病小鼠胰岛素抵抗及对骨骼肌GLUT_4蛋白表达的影响

Effect of Dahuang Huanglian Xiexin Decotion on Insulin Resistance and GLUT_4 Protein Expression of Skeletal Muscle in Mice of Type 2 Diabetes

目的:探明大黄黄连泻心汤改善2型糖尿病(Type 2 Diabetes Mellitus,T2DM)胰岛素抵抗(Insulin Resistance,IR)及作用机理。方法:昆明小鼠60只,随机分为5组:正常组(Normal,NOR),模型组(Model MOD),二甲双胍组(Metformin MET),大黄黄连泻心汤高剂量组(Dahuang Huanglian Xiexin Decotion Higher Dose,DHH)、低剂量组(Dahuang Huanglian Xiexin Decotion Low Dose,DHL),每组12只,采用高脂饲料联合腹腔注射链脲佐菌素(Streptozotocin,STZ)复制胰岛素抵抗T2DM小鼠模型。模型除正常组和模型组外,动物每天给予相应的药物进行治疗,连续14 d,末次给药后禁食12 h,眼球取血,检测空腹血糖(Fasting Blood-Glucose FBG)、空腹血清胰岛素(Fasting Insulin,FINS)、三酰甘油(Triglyceride,TG)、总胆固醇(Total Cholesterol,TC)、高密度脂蛋白(High Density Lipoprotein HDL-C)、低密度脂蛋白胆固醇(Low Density Lipoprotein Cholesterol,LDL-C)的含量,胰岛素敏感指数(Insulin Senstive Index,ISI)和胰岛素抵抗指数(Homeostasis Model Assessment-Insulin Resistance,HOMA-IR),同时采用免疫印迹法(Westernblot)法检测模型骨骼肌组织细胞膜和细胞质葡萄糖转运蛋白4(Glucose Transporter 4,GLUT_4)蛋白表达。结果:与MOD组相比,DHH、DHL组的FBG、TG、LDLC、HOMA-IR均降低,HDL-C、ISI升高,组间有显著差异(P<0.05);与MOD组相比,MET组的相关指标组间有特别显著差异(P<0.01)。与NOR组相比,模型组骨骼肌细胞膜和胞质GLUT_4蛋白表达水平下降,组间有显著差异(P<0.05);与MOD组相比,DHH、DHL和MET组的骨骼肌细胞膜和胞质GLUT_4蛋白表达水平上升,组间有显著差异(P<0.05)。结论:大黄黄连泻心汤与二甲双胍作用相似,具有较好的改善胰岛素抵抗作用,其作用机制可能与促进骨骼肌GLUT_4转位和蛋白表达有关。

Objective： To improve the mechanism of Dahuang Huanglian Xiexin Decotion on insulin resistance of type 2 diabetes mellitus. Methods： 60 kunming mice were randomly divided into 5 groups： normal group, model group, Metformin group, DHH group, DHL group, 12 in each group. Model of type 2 diabetes mices were raised with high-fat diet as well as intraperitoneal injection of STZ. In addition to the normal group and model group, other groups were given corresponding drugs for 14 days, the last fasting 12 hours after the treatment, eyeball blood was used to detect fasting blood sugar （ FBS）, serum insulin （ FINS）, three acyl glycerin （TG）, total cholesterol （TC）, high-density lipoprotein （HDL-C）, low density lipoprotein cholesterol （LDL-C） levels, insulin sensitive index （ISI） and insulin resistance index （HOMA IR）, and western blot method （Westernblot） was used to detect the ex- pression of glucose transporter 4 （ GLUT4 ） protein of skeletal muscle cell membrane and cytoplasmic of model. Results： Compared with model group, level of FBG, TG, LDL-C, HOMA-IR of group of DHH, DHL was significandy lower, and HDL-C, ISI signifi- candy higher, there was significant differences （P 〈0. 05） ; Compared with model group, there was particular significant difference of related indicators of MET group （P 〈0. 01 ） . Compared with the normal group, level of GLUT4 protein expression of skeletal mus- cle cell membrane and cytoplasm of model group was lower, there were significant differences between groups （ P 〈 O. 05） ; Compared with model group, GLUT4 protein expression of skeletal muscle cell membrane and cytoplasmic of DHH, DHL and Metformin groups was higher, there were significant differences between groups （P 〈 0. 05） . Conclusion： Dhhlxiexin Decotion has similar effect with mefformin on improving insulin resistance, its mechanism may be related to promote GLUT4 transposition and protein expression of skeletal muscle of mice.