糖脂平对胰岛素抵抗大鼠GLUT4表达的影响

Impact of Tangzhiping on GUIT4 Expression in the Rats of Insulin Resistance

目的观察糖脂平对高脂饮食诱导的胰岛素抵抗(Insulin Resistance,IR)大鼠骨骼肌细胞外膜葡萄糖转运子4(Glucose transporter 4,GLUT4)表达的影响。方法选择体重在180~200 g的雄性SD大鼠48只,随机分为空白组(12只)和造模组(36只),空白组予普通饲料喂养,造模组予高脂饲料喂养,8周造模成功后,将造模组再次随机分为:模型组、中药组、西药组,每组12只。中药组予糖脂平按生药20 g/(kg·d)灌胃,西药组予罗格列酮0.8 mg/(kg·d)灌胃,模型组和空白组灌服等量的生理盐水,持续8周,末次给药后禁食12 h,用正常血糖高胰岛素钳夹实验评价胰岛素敏感性(M值);酶法检测各组大鼠总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-c)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-c);蛋白印记法(Western Blot,WB)检测骨骼肌细胞外膜GLUT4的表达。结果与空白组比较,模型组大鼠胰岛素敏感性明显降低,血清TC、TG、LDL-c均明显升高,HDL-c明显降低,骨骼肌细胞外膜GLUT4表达明显减少(P<0.05);与模型组比较,中药组大鼠胰岛素敏感性明显提高,TG、LDL-c水平降低,骨骼肌细胞外膜GLUT4的表达明显增多(P<0.05),对TC、HDL-c无明显影响(P>0.05)。结论糖脂平具有提高IR大鼠胰岛素敏感性、调节脂代谢紊乱的作用,其作用机制可能与提高细胞外膜GLUT4的表达,增加骨骼肌组织对葡萄糖的摄取和利用有关。

Objective To observe the impacts of tangzhiping on GLUT4 expression of epicyte of skeletal muscle in the rats of insulin resistance induced by high- lipid diet. Methods Forty- eight male SD rats,weighted from 180 to 200 g were selected and randomized into a blank group( 12 rats) and a modeling group( 36 rats). In the blank group,the common forage was used. In the model group,the high- lipid forage was used. After successful modeling in 8 weeks,the rats in the modeling group was subdivided randomly into a mode group,a Chinese medicine group and a western medicine group,12 rats in each one. In the Chinese medicine group,tangzhiping was used for gavage,20 g / kg a day. In the western medicine group,rosiglitazone was used for gavage,0. 8 mg / kg a day. The physical saline of same dose was used for gavage in the model group and the blank group. The gavage lasted for 8 weeks continuously. After the last medication,fasting was done for 12 h. The euglycemic hyperinsulinemic clamp technique was performed to evaluate the insulin sensitivity( M value). Enzymatic detection was used to measure the levels of TC,TG,HDL- C and LDL- C.Western Blot was used to detect GLUT4 expression of epicyte of skeletal muscle. Results Compared with the blank group,the insulin sensitivity was apparently reduced,the levels of TC,TG and LDL- C were apparently increased,HDL- C and GLUT4 expression were apparently reduced in the model group. Compared with themodel group,the insulin sensitivity was increased apparently,the levels of TG and LDL- C were reduced,GLUT4 expression was increased apparently in the Chinese medicine group. The changes in TC and HDL- C were not apparent. Conclusion Tangzhiping improves the insulin sensitivity and adjusts lipid metabolic disturbance in the rats of insulin resistance. The effect mechanism may be related to the improvement of GLUT4 expression in epicyte of skeletal muscle and enhancement of the absorption and utility of skeletal muscular tissue to glucose.