缺氧you导因子-1α论文：缺氧you导因子-1在肾间质纤维化中的表达及意义.docVIP

缺氧诱导因子-1α论文：缺氧诱导因子-1在肾间质纤维化中的表达及意义 【中文摘要】探讨缺氧诱导因子-1α(hypoxia-inducible factor-la, HIF-la)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(sham-operated rats, SOR)和单侧输尿管梗阻(ulilateral ureteral obstruction, UUO)模型组。各组3天,7天,14天处死大鼠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实时荧光定量RT—PCR法检测肾脏组织中HIF-1αCTGF, TGF-β1蛋白和mRNA表达。结果：(1)HE染色结果显示：UUO组与SOR组比较,肾组织的损害程度逐渐加重,UUO组3天肾间质水肿,肾小管出现扩张,少量炎细胞浸润间质区,7天上述变化更加明显：间质区明显变宽,扩张的肾小管有不同程度的萎缩和坏死,上皮细胞空泡变性、脱落、坏死,14天炎细胞广泛浸润肾间质区,肾间质纤维化进行性加重。(2)免疫组化结果显示：HIF-1α, CTGF, TGF-β1蛋白表达逐渐增加,CTGF和HIF-1α主要表达于间质细胞与肾小管上皮细胞,TGF-β1主要表达于肾间质细胞。(3)RT-PCR结果显示：在术后第3天HIF-1αmRNA表达开始增加,CTGF, TGFβ1mRNA水平也随之逐渐增加,且与假手术组相比HIF-1α, CTGF, TGF-β1mRNA表达水平均有统计学意义(P0.05)。(4)相关性分析：模型3天组HIF-1αmRNA表达与CTGF mRNA, 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-lamRNA分别和CTGF mRNA、TGFβ1mRNA呈正相关(分别为r=0.663,0.645,P0.05),模型组第14天组HIF-1αmRNA分别和CTGF mRNA、TGFβ1mRNA呈正相关(分别为r=0.515,0.752)。结论：HIF-1α可能通过调节TGF-β1与CTGF的表达参与了肾间质纤维化的病理过程。 【英文摘要】:To investigate the role of hypoxia-inducible factor-1a (HIF-la) 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-la、CTGF、TGF-β1 were assayed by immunohistochemistry and real time polymerase chain reaction.Results:(1)HE stain:Renal damage was exacerbated in UUO group compared with those of sham group. At 3th day after UUO, the renal interstitial edema was found, tubular expanded and inflammatory cells existed in tubulointerstitial. The change became obviously at the 7 th day:interstitial obviously widend,expansion had degenerated, had odema and some even died, on the 14 th day, substantial inflammatory cell infiltrated and renal interstitial fibrosis aggravated. (2)immunohistochemistry:the protein expression of HIF-1a、CTGF and TGF-β1 were all sign