【摘要】 目的:探讨复方中药黄芪当归合剂(A&A)对残余肾慢性肾衰竭大鼠的抗肾纤维化疗效。方法:采用5/6肾切除制备残余肾慢性肾衰竭大鼠模型,以血管紧张素转换酶抑制剂类药物依那普利(enalapril,Ena)作为阳性对照药物,将Wistar大鼠随机分为假手术组(sham组)、5/6肾切除术模型组(Model组)、A&A治疗组(A&A组,给予生药每天每千克体重各12g)和Ena治疗组(Ena组,给予Ena每天每千克体重4mg)。于造模后第2、4、8、12周分析各组动物尿蛋白、血清肌酐及尿素含量,光镜下观察肾组织病理改变并测定肾小球面积,免疫组化检测肾皮质纤维连接蛋白(FN)、Ⅳ型胶原(Col-Ⅳ)在肾小球和肾间质的表达情况。结果:与sham组相比,造模后Model组肌酐及尿素增高;每日尿蛋白量持续增多;肾病理显示肾小球增大、渐进性肾小球系膜细胞及系膜基质增多及肾小球硬化,造模后第8和12周肾小球内FN及Col-Ⅳ积聚显著增加。与Model组相比,A&A组在第2、4、8和12周具有降低尿蛋白的作用,尿蛋白分别减少34%、44%、25%和45%(P均<0.05)。A&A治疗后第8周时肾小球系膜细胞增生和系膜基质积聚明显减少,肾组织中FN和Col-Ⅳ表达分别减少18%和29%(P均<0.05);第12周时硬化肾小球数目显著减少,肾间质纤维化病变明显减轻,肾组织中FN和Col-Ⅳ表达分别减少17%和14%(P均<0.05);但A&A并未能改善肾功能。A&A疗效与Ena基本相同。结论:在残余肾慢性肾衰竭大鼠模型中,A&A具有减少细胞外基质成分沉积、减轻肾小球硬化和肾间质纤维化病变的肾保护作用,其疗效可能是通过其早期开始并持续降低尿蛋白的肾损伤作用而实现的。更多还原

【Abstract】 Objective:To explore whether Chinese herbs Astragalus and Angelica mixture(A&A) have renoprotective effects on chronic renal failure in rats.Methods:5/6 nephrectomized kidney in rats was used as chronic renal failure model.Rats were randomly divided into four groups which included sham,Model,A&A and enalapril(Ena) groups.The remnant kidney was harvested after 2,4,8,12 weeks,and levels of serum creatinine(scr),urea and urinary protein excretion were measured using routine biochemical methods.The pathological lesions were observed by light microscope.The expressions of fibronectin(FN) and collagen Ⅳ(Col-Ⅳ) in glomeruli and interstitium were detected by immnuohistochemistry.Results:5/6 nephrectomized rats were presented with the characteristics of increasing scr and urea,persistent proteinuria at the end of the 2nd,4th,8th,12th weeks,respectively.They had increasing size of glomeruli with progressive proliferation of mesangial cells and mesangial matrix followed by glomerulosclerosis and progressive elevated expressions of FN and Col-Ⅳ.Compared with Model group,the administration of A&A could decrease urinary protein excretion for 34%,44%,25%,45% at the end of the 2nd,4th,8th and 12th weeks,respectively(P<0.05).At the end of the 8 th week of A&A administration,mesangial proliferation was much lower than that in the untreated rats,the expressions of FN and Col-Ⅳ were decreased for 18% and 29%(P<0.05),respectively.At the end of the 12th week,the number of sclerotic glomeruli was decreased and renal interstitial fibrosis almost disappeared,accompanied with the decreased expressions of FN and Col-Ⅳ for 17% and 14%(P<0.05),respectively.The beneficial effects of A&A were similar to the effects of enalapril in the study.Conclusion:A&A reduced extracellular matrix deposition and down-regulated the lesions of glomerulosclerosis and renal interstitial fibrosis in rats with chronic renal failure,which may be due to its effect on the earlier and persistent reduction of proteinuria.更多还原