【摘要】 目的探讨大鼠阿霉素肾病(ADR)肾组织转化生长因子β1(TGF-β1)、血小板源性生长因子-BB(PDGF-BB)、结缔组织生长因子(CTGF)的表达与肾间质纤维化的关系及莫索尼定对其影响。方法2004年8月至2004年11月选取哈尔滨医科大学动物实验中心的60只雄性健康Wistar大鼠随机分为健康对照组、模型组及莫索尼定(MOX)治疗组,两次阿霉素尾静脉注射建立模型,治疗组给予MOX1·5mg/(kg·d);分别于4、8、12周末留取标本,测定24h蛋白尿、血生化、肾组织分别进行透射电镜及HE、Mas-son染色,应用免疫组织化学方法检测肾组织中的TGF-β1、PDGF-BB、CTGF蛋白的表达。结果血压、生化指标在治疗组和模型组差异无显著性,模型组24h尿蛋白排泄率高于对照组,差异有显著性(P<0·05),治疗组24h蛋白尿明显低于模型组,差异有显著性(P<0·05),与对照组比较模型组肾小管、肾间质呈明显病理改变,差异有显著性(P<0·05),治疗组损伤较模型组减轻,差异有显著性(P<0·05)。PDGF-BB蛋白表达于第4周,TGF-β1、CTGF蛋白表达第8周开始明显上调,与肾间质纤维化程度呈正相关,莫索尼定治疗组上述生长因子表达下调,差异均有显著性(P<0·05)。结论在大鼠阿霉素肾病肾组织中,肾间质纤维化与TGF-β1、PDGF-BB、CTGF蛋白高表达有关,莫索尼定通过下调促纤维化因子的表达,从而发挥其延缓肾纤维化及肾小球硬化作用。更多还原

【Abstract】 Objective To investigate the expression of transforming growth factor β₁（TGF-β₁）、platelet-derived growth factor-BB（PDGF-BB）、connective tissue growth factor（CTGF）in rats with adriamycin-induced nephropathy（ADR）and tubulointerstitial fibrosis and the effect of moxonidine.Methods From Aug.2004 to Nov.2004,60 rats were randomly assigned as healthy group,model group and treatment group.Fifty rats received twice-intravenous injection of adriamycin.Treatment group was given moxonidine for a dose of 1.5 mg/（kg·d）.The samples were collected at the end of 4th week,8th week and 12th week.Proteinuria and some biochemical values in serum were assayed and the kidney morphology was investigated at the end of the experiments.Immunohistochemistry was used to detect the expression of TGF-β₁,PDGF-BB and CTGF.Results Bp and biochemical values in serum were not significantly different between model group and treatment group.Urine albumin excretion rate was significantly lower in moxonidine treated compared with untreated rats（P<0.05）.The indices of renal and tubular damage and tubulointerstitial fibrosis were significantly higher in model group than those of treatment and control group（P<0.05）.In the treatment group,the expression of PDGF-BB was up-regulated at the end of 4th week and the expression of TGF-β₁,CTGF and PDGF was upregulated at the end of 8th.They had positive relationship with tubulointerstitial fibrosis.But those factors were down-regulated in moxonidine treated group.Conclusion For ADR,tubulointerstitial fibrosis is concerned with the up-regulating of the expression of TGF-β₁,PDGF-BB and CTGF.Our findings demonstrate that moxonidine confers a protective effect on renal and tubulointerstitial injury through down-regulation of the protein expression of TGF-β₁,PDGF-BB and CTGF.更多还原