【摘要】 目的探究加味芪黄饮治疗糖尿病肾病(DN)的作用及其机制。方法采用高脂饮食联合腹腔注射链脲佐菌素的方法制备DN大鼠模型,随机分为:正常组、模型组、加味芪黄饮低剂量组和高剂量组,低、高剂量组大鼠每日分别予加味芪黄饮400 mg/kg、800 mg/kg灌胃治疗。12周后检杀,留取大鼠血、尿标本测定24 h尿白蛋白(24 h UAlb)、血肌酐(Scr)、尿素氮(BUN)、空腹血糖(FBG)、空腹胰岛素(FIns)、胰岛素抵抗指数(HOMA-IR)等指标,观察肾组织病理改变并行系膜增生指数(MEI)评分,免疫组化观察肾组织中胰岛素受体(InsR)、胰岛素受体底物-1(IRS-1)、磷脂酰肌醇-3-激酶(PI3K)、葡萄糖转运体4(GLUT4)等蛋白表达。结果与正常组比较,模型组大鼠24 h UAlb、Scr、BUN、FBG、FIns、HOMA-IR均明显升高(P<0.01),肾小球肥大,肾小球基底膜、系膜细胞、系膜基质弥漫增生,MEI评分升高(P<0.01);低、高剂量组大鼠上述指标均较模型组降低(P<0.05),肾组织病理损伤及MEI评分均较模型组改善(P<0.05),均呈剂量依赖性。与正常组比较,模型组大鼠肾组织中InsR、IRS-1、PI3K、GLUT4等蛋白表达下调(P<0.05);低、高剂量组大鼠上述蛋白表达均较模型组升高(P<0.05),且随药物剂量增加其升高趋势更明显。结论加味芪黄饮能延缓DN进展,其机制可能是通过激活InsR/IRS-1/PI3K/GLUT4通路,改善胰岛素抵抗状态发挥作用。更多还原

【Abstract】 Objective To explore the effect and mechanism of Jiawei Qihuang Yin in diabetic nephropathy( DN). Methods The male Sprague-Dawley rats were randomly divided into the normal group,DN group,and Jiawei Qihuang Yin low-and high-dose groups. The rats in low-and high-dose groups were treated with Jiawei Qihuang Yin in 400 mg/kg and 800 mg/kg,respectively. Rats were sacrificed after 12 weeks and the blood and urine were collected to detect the 24-hour urinary albumin( 24 h UAlb),serum creatinine( Scr),blood urea nitrogen( BUN),fasting blood glucose( FBG),fasting insulin( FIns) and homeostasis model assessment of insulin resistance( HOMA-IR). Kidney tissues were harvested and stained with Hematoxylin-eosin and were graded for mesangial expansion index( MEI). Immunohistochemistry was applied to observe the expression of insulin receptor( InsR),insulin receptor substrate-1( IRS-1),phosphoinositide 3-kinase( PI3 K),glucose transporter 4( GLUT4) in renal tissue. Results The levels of the 24 h UAlb,Scr,BUN,FBG,FIns and HOMA-IR were significantly increased in DN group compared with the normal group( P<0.01). All the indexes above were apparently decreased after intervention with Jiawei Qihuang Yin( P < 0. 05). Glomerular hypertrophy was observed in DN rats,accompanied with diffused proliferation of glomerular basement membrane,mesangial cells and mesangial matrix. Moreover,MEI scores were obviously elevated in DN rats( P<0.01). The pathological injury and MEI were improved by Jiawei Qihuang Yin treatment( P<0.05). The levels of InsR,IRS-1,PI3 K and GLUT4 were reduced in DN group in comparison with normal group( P < 0. 05). Treatment with Jiawei Qihuang Yin elevated the expression of these proteins( P < 0. 05). Conclusion Jiawei Qihuang Yin plays a treatment role in DN,which may improve the state of insulin resistance via InsR/IRS-1/PI3 K/GLUT4 pathway.更多还原