论文部分内容阅读
目的制作大鼠慢性马兜铃酸肾病模型,初步探讨该模型肾间质纤维化的发病机制。方法雄性SD大鼠随机分为2组,模型组给关木通浸膏水溶液间断灌胃,对照组仅给自来水灌胃。灌胃后第4、8和12周每组各处死6只大鼠,留取两侧肾脏,应用实时定量反转录聚合酶链反应(realtimequantitativeRT-PCR)和免疫组织化学方法研究两组大鼠肾脏Ⅰ型胶原(ColⅠ)、转化生长因子-β1(TGF-β1)、结缔组织生长因子((CTGF)、纤溶酶原激活物抑制物-1(PAl-1)和金属蛋白酶组织抑制物-1(TIMP-1)的mRNA及蛋白质表达。结果模型组大鼠用药后第4周肾实质ColⅠ、TGF-β1、CTGF、PAI-1及TIMP-1mRNA表达显著上调,分别达对照组的9.31倍、5.16倍、1.79倍、8.66倍及2.54倍(P<0.01或P<0.05);第8周除TIMP-1有所升高外其余指标mRNA表达均有所下降,但与对照组比较差异仍有统计学意义(P<0.01或P<0.05);第12周全部指标mRNA表达继续下降,除CTGF外其余指标与对照组比较差异仍有统计学意义(P<0.01或P<0.05)。模型组大鼠用药后第4周ColⅠ、TGF-β1、CTGF、PAI-1及TIMP-1在肾小管间质的阳性染色面积显著扩大,分别达对照组的2.24倍、1.43倍、1.13倍、1.17倍及1.24倍(P<0.01),第8周和第12周全部指标阳性染色面积持续扩大(P<0.01)。结论慢性马兜铃酸肾病大鼠肾间质?
OBJECTIVE: To establish a rat model of chronic aristolochic acid nephropathy and to explore the pathogenesis of renal interstitial fibrosis in this model. Methods Male Sprague-Dawley rats were randomly divided into 2 groups. The model group was administered gavage of aqueous solution of Guanmutong extract intermittently, and the control group was given gavage only with tap water. At the 4th, 8th and 12th weeks after gavage, 6 rats were sacrificed in each group, and the kidneys of both sides were collected. Realtime quantitative RT-PCR and immunohistochemical staining The expression of Col Ⅰ, TGF-β1, CTGF, PAI-1, and tissue inhibitor of metalloproteinase- 1 (TIMP-1) mRNA and protein expression.Results The expression of ColⅠ, TGF-β1, CTGF, PAI-1 and TIMP-1mRNA in renal parenchyma in model group were significantly up-regulated by 9.31-fold , 5.16-fold, 1.79-fold, 8.66-fold and 2.54-fold respectively (P <0.01 or P <0.05). At the 8th week, the mRNA expression of all other indexes decreased except TIMP- (P <0.01 or P <0.05). The mRNA expression of all the indexes continued to decline at the 12th week, and there was still significant difference between the other indexes except CTGF and the control group (P <0.01 or P <0.05) The positive staining area of ColⅠ, TGF-β1, CTGF, PAI-1 and TIMP-1 in tubulointerstitial were significantly enlarged in the 4th week after treatment in rats in the control group .24, 1.43, 1.13, 1.17 and 1.24 folds (P <0.01). The positive staining area of all the indexes in the 8th week and the 12th week continued to expand (P <0.01) .Conclusion Chronic aristolochic acid nephropathy rats Renal interstitial?