摘要
目的探讨黄芪甲苷(AS-Ⅳ)对糖尿病大鼠肝脏损伤的保护作用及其可能机制。方法采用腹腔注射链脲佐菌素诱导建立糖尿病大鼠模型。将造模成功的糖尿病大鼠随机分为对照组、模型组、罗格列酮组(1.25 mg/kg)、AS-Ⅳ组(20、40、80 mg/kg)。连续灌胃给药6周,于给药前测空腹血糖,处死,取肝脏,称肝湿重,计算肝脏指数;采用ELISA法测定各组大鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性;试剂盒检测肝脏组织中谷胱甘肽过氧化物酶(GSH-Px)、总超氧化物歧化酶(T-SOD)和丙二醛(MDA)含量变化;HE染色观察肝组织病理形态学变化;免疫组化法检测肝脏组织中胰岛素受体底物2(IRS-2)的表达;Western blot法检测磷脂酰肌醇-3-激酶(PI3K)、磷酸化蛋白激酶B(p-AKT)和葡萄糖转运蛋白4(GLUT4)的表达水平。结果与对照组相比,模型组大鼠肝脏指数、空腹血糖、空腹血清胰岛素、血清AST、ALT、三酰甘油、总胆固醇、高密度脂蛋白水平、肝脏组织中MDA含量均明显升高(P<0.01),T-SOD与GSH-Px降低(P<0.01),肝病理损伤明显,同时肝组织中IRS-2、PI3K、p-AKT、GLUT4蛋白表达减少。与模型组相比,AS-Ⅳ(20、40、80 mg/kg)组能明显改善上述指标的变化,使肝组织损伤减轻,并增加IRS-2、PI3K、pAKT、GLUT4蛋白表达。结论 AS-Ⅳ对糖尿病大鼠肝损伤有保护作用,其机制可能与抗氧化、上调肝脏PI3K/AKT信号通路有关。
Objective To investigate the protective effect of astragaloside Ⅳ（ AS-Ⅳ） on liver injury in diabetic rats and its potential mechanism. Methods Diabetic rats model was established by intraperitoneally injecting streptozotocin. The diabetic rats were randomly divided into control group,model group,rosiglitazone group（ 1. 25 mg/kg） and AS-Ⅳ groups（20,40,80 mg/kg）. Intragastric administration for 6 weeks,measured fasting blood glucose before dosing,then executed the rats,take the liver,weighed the liver wet weight,calculated the liver index. The levels of alanine aminotransferase（ ALT） and aspartate aminotransferase（ AST） in the serum were detected by enzyme-linked immunosorbent assay. The active of Glutathione peroxidase（ GSH-Px）,total superoxide dismutase（ TSOD） and malondialdehyde（ MDA） in liver tissue were detected according to the kit instructions. According to the kit instructions. The pathological changes of liver tissue in rats were observed by hematoxylin and eosin staining.The protein expression level of insulin receptor substrate 2（ IRS-2） in liver tissue was detected by immunohistochemistry method. The protein expression levels of PI3 K,p-AKT and GLUT4 by Western blot analysis. Results Compared with the normal group,the model group liver index,fasting blood glucose,fasting insulin,serum AST,ALT,triglyceride,total cholesterol,highdensity lipoprotein and the content of MDA in liver tissue were significantly increased（ P〈0. 01）,T-SOD and GSH-Px were decreased（ P〈0. 01）. Liver pathological injury was obvious and the protein expression levels of IRS-2,PI3 K,p-AKT,GLUT4 in liver tissue were decreased. Compared with the model group,AS-Ⅳ（20,40,80 mg/kg） group significantly improved the above indexes,reduced the injury of liver tissue and increased the protein expression levels of IRS-2,PI3 K,p-AKT and GLUT4. Conclusion AS-Ⅳ has protective effect on liver injury in diabetic rats and the mechanism underlying. And the mechanism underlying may be related to anti-oxidative and up-regulation of PI3 K/AKT signal pathway in liver.
出处
《安徽医科大学学报》
CAS
北大核心
2017年第12期1823-1829,共7页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81173624)
安徽省国际合作项目(编号:12030603007)
安徽省教育厅自然科学基金(编号:KJ2016SD35)
