加味芪黄饮对糖尿病肾病的作用及其机制研究

The Effect and Mechanism of Jiawei Qi Huang Yin on Diabetic Nephropathy

目的研究加味芪黄饮治疗糖尿病肾病(DN)的作用及其机制。方法雄性SD大鼠60只,随机分成正常对照组、模型对照组及加味芪黄饮低、高剂量组(400、800 mg·kg-1·d-1)。以高糖高脂饮食及链脲佐菌素复制DN大鼠模型。给药12周后,测定各组大鼠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)、胰岛素敏感指数(ISI)等指标,HE染色观察大鼠肾组织病理改变,Western Blot法检测大鼠肾组织中胰岛素受体底物-1(IRS-1)的表达。结果与模型对照组比较,加味芪黄饮低、高剂量组大鼠24 h UAlb、Scr、BUN、FBG、FINS水平均较明显降低(P<0.05),ISI则明显升高(P<0.05),且有一定的量效关系;能减轻DN大鼠肾小球肥大,系膜细胞、系膜基质弥漫增生等病理改变;使大鼠肾组织IRS-1表达明显升高(P<0.05)。结论加味芪黄饮能保护DN大鼠的肾功能,减轻DN大鼠肾组织损伤,其可能通过上调IRS-1表达,以改善胰岛素抵抗状态而发挥作用。

Objective To investigate the effect and mechanism of Jiawei Qi Huang yin on diabetic nephropathy.Methods The male Sprague-Dawley rats were randomly divided into 4 groups including normal group,DN group,Jiawei Qi Huang yin low-and high-dose group(the DN rats were treated with the traditional Chinese medicine for 12 weeks respectively in 400 mg·kg·d-1 or 800 mg·kg·d-1).After 12 weeks,the blood and urine were collected to detect the 24 h urinary albumin(24 h UAlb),serum creatinine(Scr),blood urea nitrogen(BUN),fasting blood glucose(FBG),fasting insulin(FINS)and insulin sensitivity index(ISI),and then the rats were sacrificed.The pathologic morphology of rats were observed by the HE staining.Western Blot was applied to detect protein level of insulin receptor substrate-1(IRS-1)in rats’renal tissue.Results It shows that the 24 h UAlb,Scr,BUN,FBG and FINS were significantly decreased in the Jiawei Qi Huang yin groups compared with the DN group(P<0.05),while the ISI was significantly increased(P<0.05).The trend was more obvious following the increase of Jiawei Qi Huang yin dose.Compared with the normal control group,the rats in DN group showed glomerular hypertrophy,diffuse proliferative mesangial cells and mesangial matrix and stenosis of kidney tubules.Jiawei Qi Huang yin can alleviate the renal damage described above,increase IRS-1 protein expression level in rats’renal tissue(P<0.05).Conclusion Jiawei Qi Huang yin is effective in the treatment of diabetic nephropathy.It probably acts through improving the state of insulin resistance by up-regulating IRS-1 expression.