苦参素防治阿霉素肾病鼠肾小球硬化

Experimental study of oxymatrine in preventing glomerulosclerosis in rats with adriamycin-induced nephropathy

目的:观察苦参素(OM)对阿霉素肾病鼠慢性肾脏损害的长期保护作用,并探讨其可能的作用机制.方法:60只Wistar大鼠随机分为4组:正常对照组,OM50mg/(kg·d)治疗组,OM100mg/(kg·d)治疗组,模型组.采用阿霉素分次尾静脉注射构建肾病慢性进展模型.各干预组予以相应的剂量进行灌胃,每隔8wk杀检一批大鼠观察尿蛋白、血清尿素氮、肌酐及肾脏病理指标的改变,并用免疫组化法检测肾组织转化生长因子β1(TGF-β1),Smad1,2,3,5,Smad7蛋白的表达.结果:各干预组比模型组尿蛋白排泄量明显减少,血肌酐和尿素氮水平下降,肾小球系膜增生、硬化程度明显减轻;肾小球内TGF-β1和Smad1,2,3,5沉积较模型组明显减少,Smad7的沉积较模型组明显增多.结论:OM对阿霉素肾病鼠的慢性肾脏损害有一定的保护作用,OM抗肾纤维化的作用可能与干预TGF-β1/Smads信号传导通路有关.

AIM： To observe the long-term renoprotective effects of oxymatrine on the adriamycin-induced nephropathy rats with chronic progressive renal lesions, and explore its mechanisms. METHODS： The experiments were performed on 60 male Wistar rats. The rats were randomly divided into 4 groups： normal control group, oxymatrine 50 mg/（ kg· d ） treatment group, oxymatrine 100 mg/（ kg · d ） treatment group, model group. Adriamycin （2 mg/kg） was intravenously administered twice at a 21-day interval. Oxymatrine was used for gastric perfusion from the 1 st day after the second injection of adriamycin until the end of the study. After 7 weeks, 5 rats in each group were sacrificed every 8 weeks for blood biochemical analyses and histological study. Urinary protein （ mg/24 h）, the concentrations of serum creatinine （Cr） and blood urea nitrogen （BUN） were checked with automatic biochemistry analyzer, and a semiquantitative score was used to evaluate the degree of glomerular lesions. Finally, immunohistochemistry was to examine the expression of transforming growth factor-β （TGF-β）, Smadl, 2, 3, 5 and Smad7 in glomendi. RESULTS： Oxymatrine not only reduced urinary protein, Cr and BUN in blood, but also significantly ameliorated glomerular sclerosis and mesangial proliferation. Meanwhile, immunohistochemistry staining indicated that TGF-β1, Smadl, 2, 3, 5 expressions increased and Smad7 expression decreased in model group as compared with the 2 treatment groups. CONCLUSION： Oxymatrine has a renoprotective effect on the adriamycin-induced nephropathy rats with chronic progressive renal lesions, and its mechanism is considered to be relevant to intervention of the pathway of signal conduction of TGF-β1/ Smads.