摘要
目的:探讨缺氧诱导因子-1α(HIF-1α)致肾间质纤维化的作用。方法:60只雄性SD大鼠随机分为假手术组(SOR)和单侧输尿管梗阻(UUO)模型组。术后第3天,第7天,第14天各处死大鼠10只,肾组织行HE染色并观察病理变化。采用免疫组织化学和荧光定量逆转录聚合酶链反应(Q-RT-PCR)法检测肾脏组织中HIF-1α、CTGF、TGF-β1蛋白和mRNA表达。结果:与假手术组相比,模型组大鼠肾脏病理损害进行性加重;HIF-1α、CTGF、TGF-β1蛋白表达随梗阻时间的延长逐渐增加;与假手术组相比HIF-lα、CTGF、TGF-β1mRNA表达明显增加(P<0.05);相关分析显示,模型组第3天HIF-lαmRNA表达与CTGFmRNA,TGF-β1mRNA表达分别呈正相关(r=0.748,0.659,P<0.05),模型组第7天组HIF-1αmRNA分别和CTGFmRNA、TGF-β1mRNA呈正相关(分别为r=0.663,0.645,P<0.05),模型组第14天组HIF-1αmRNA分别和CTGFmRNA、TGF-β1mRNA呈正相关(分别为r=0.515,0.752,P<0.05)。结论:HIF-1α可能通过调节CTGF、TGF-β1的表达参与了肾间质纤维化发生和发展的过程。
Objective:To investigate the role of hypoxia-inducible factor-1α (HIF-1α) on renal fibrosis.Methods:60 Sprague-Dawley male rats were randomly divided into sham-operated rats group (SOR group) and ulilateral ureteral obstruction model group (UUO group).Ten rats were killed 3,7,and 14 days after operation respectively,the dynamic histological changes of renal interstitial tissues were observed on HE stained tissue sections.The expression of protein and mRNA of HIF-1α、CTGF、TGF-β1 were assayed by immunohistochemistry and real time polymerase chain reaction.Results:Renal damage was exacerbated and the protein expression of HIF-1α、CTGF and TGF-β1 were all significantly increased in UUO group compared with those of sham group;Real time PCR showed significantly increased expression of HIF-lα 、CTGF 、TGF-β1 mRNA in the UUO group than the sham group (P0.05).There was positive correlation between the expression of HIF-lα mRNA and CTGFmRNA、TGF-β1 mRNA in UUO day 3 group(r=0.748,0.659 P0.05).Conclusion:HIF-1α may promote the development process of the renal interstitial fibrosis through regulating the expression of CTGF and TGF-β1.
出处
《中国中西医结合肾病杂志》
2012年第1期18-21,I0004,共5页
Chinese Journal of Integrated Traditional and Western Nephrology