黄金胶囊改善糖尿病大鼠胰岛素抵抗与PI-3K,GLUT4蛋白的表达

目的:研究黄金胶囊对糖尿病(DM)大鼠磷脂酰肌醇3激酶(PI-3K),葡萄糖转运因子4(GLUT4)在肝脏及骨骼肌组织中的蛋白表达,并探讨其改善大鼠血糖的可能机制。方法:SPF级雄性Wistar大鼠65只,血糖在4.77~7.77 mmol·L~(-1)的大鼠入选,入选大鼠60只,正常组12只外,其余大鼠采用高脂饲料喂养联合小剂量链脲佐菌素ip的方法,建立DM大鼠模型。将造模成功大鼠随机分为黄金胶囊组(2.025 g·kg~(-1)),罗格列酮组(0.36 mg·kg~(-1)),模型组,继续高脂饲料喂养,并予以相应药物ig治疗10周,其中模型组与正常组均予以生理盐水ig,观察大鼠一般状态,体重及摄食量,干预10周后,予10%水合氯醛麻醉大鼠,检测大鼠空腹血糖(FBG),空腹胰岛素(FINS)及胰岛素敏感指数(ISI)。采用苏木素-伊红(HE)检测各组大鼠肝脏、骨骼肌组织的病理改变及免疫组化检测PI-3K和GLUT4蛋白的表达。结果:与正常组比较,模型组DM大鼠FBG,FINS水平明显升高,ISI水平明显降低,肝脏及骨骼肌组织中PI-3K,GLUT4蛋白表达明显降低(P0.05),病理学检测发现大鼠肝脏、骨骼肌组织的病变较为明显;与模型组比较,药物干预后,黄金胶囊组与罗格列酮组均可降低DM大鼠的FBG,FINS水平,提高ISI水平,明显升高肝脏及骨骼肌组织中PI-3K,GLUT4蛋白表达(P0.05),大鼠肝脏、骨骼肌组织的病变明显改善。结论:黄金胶囊提高胰岛素敏感性的作用,与激活肝脏及骨骼肌组织胰岛素信号传导通路中PI-3K和GLUT4的蛋白表达有关。

Effect of Huangjin Capsule in AlleviatingInsulin Resistance and Protein Expression of PI-3K and GLUT4 in Type 2 Diabetic Rats

Objective: To study the effect of Huangjin capsule on protein expressions of phosphatidylinositol-3-kinasem(PI-3K),glucose transporter 4(GLUT4) in liver and skeletal muscle tissue of diabetes mellitus and insulin resistance rats. Method: Totally 65 SPF male Wistar rats with the blood glucose ranging between 4.77-7.77 mmol·L^-1.Except the 12 rats in normal group, all of the remaining rats were given high-fat diet and 1%streptozotocin 50 mg·kg^-1 to build the rat model of diabetes mellitus. The diabetic rats were randomly divided into Huangjin capsule group(Huangjin capsule suspension, 2.025 g·kg^-1), rosiglitazone (rosiglitazone suspension, 0.36 mg·kg^-1). Model group was continuously fed with high-fat diet, andtreated by the corresponding drugs together with normal group for 10 weeks. Both model group and normal group were given normal saline. The general state of the rats, body weight and food intake were observed. 10 weeks later after the intervention,10%chloral hydrate was injected to anesthetize the rats totest fasting blood-glucose(FBG), fasting insulin(FINS), and insulin sensitivity index(ISI). The immunochemical method was used to detect the pathological changes in rat liver and skeletal muscle tissue, and HE was applied to detect PI-3K and GLUT4 protein expressions. Result: Compared with normal group, model group showed significant increases in FBG, FINS levels, and decreases in ISI, PI-3K and GLUT4 protein expressions in rat liver and skeletal muscle tissue (P<0.05), and the pathological detection showed obvious lesions in rat liver and skeletal tissue.After drug intervention, compared with model group, both Huangjin capsule group and rosiglitazone group can reduce the level of FBG and FINS of diabetes mellitus and insulin resistance rats, increase the level of ISI,PI-3K and GLUT4 protein expressions in rat liver and skeletal muscle tissue(P<0.05), with obvious alleviation in lesions in rat liver and skeletal tissue. Conclusion: Huangjin capsule has the effect in improving insulin sensitivity, the mechanism is correlated with the activation of PI-3K and GLUT4 protein expression in insulin signal pathway of skeletal muscle tissue.