雌激素对单侧输尿管梗阻大鼠肾间质纤维化的保护作用

Renal protective effect of estrogen on renal interstitial fibrosis after unilateral ureteral obstruction in rats

目的探讨雌激素对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的作用。方法雌性SD大鼠30只,随机分为4组:I组对照组;Ⅱ组生理雌激素组;Ⅲ组低雌激素组;Ⅳ组高雌激素组。UUO术后21 d处死各组大鼠,光镜观察梗阻肾组织病理变化,并分别用免疫组化和RT- PCR方法检测各组肾组织α-平滑肌肌动蛋白(α-SMA)和金属蛋白酶1组织抑制剂(TIMP-1)的表达。结果低雌激素组间质纤维化病变最明显,高雌激素组病变显著减轻(P<0．01)。与生理雌激素组相比,低雌激素组α-SMA和TIMP-1蛋白和基因的表达增加(P<0．05);高雌激素组上述物质表达则减少(P<0．05)。结论雌激素可能通过抑制α-SMA和TIMP-1的表达进而减少细胞外基质的沉积而发挥肾保护作用。

Objective To investigate the effect of 17-β-estradiol on renal interstitial fibrosis after unilateral ureteral obstruction（UUO） in rats. Methods Thirty female Sprague-Dawley rats were randomly divided into four groups ： （ Ⅰ ） control group ： rats were treated with sham operation ; （ Ⅱ ） normal estrogen group： rats underwent UUO; （Ⅲ）low estrogen group： rats were ovariectomized （OVX） and underwent UUO; （Ⅳ） high estrogen group： rats underwent UUO and received 17-β- estradiol injection. Rats were sacrificed at day 21 after UUO operation, and the renal tissues were examined by HE, PAS, Masson and PASM stain. Immunohistochemistry and reverse transcriptionpolymerase chain reaction were applied to determine the protein and mRNA expression of α-SMA and TIMP-1. Results Tubulointerstifial fibrosis was found in group Ⅱ .Compared with group Ⅱ , the lesion was remarkably aggravated in group Ⅲ （P 〈 0.05） and was attenuated in group Ⅳ （P 〈 0.05）. Compared with control group, the expression of protein and mRNA of α-SMA and TIMP-1 increased significantly in UUO groups （P 〈 0.01）. Compared with group Ⅱ , the expression of protein and mRNA of α-SMA and TIMP-1 in group Ⅲ increased significantly （P 〈 0.05）,which decreased significantly in group Ⅳ （P 〈 0.05）. Conclusion Estrogen may protect the kidney through the inhibition of expression of α-SMA and TIMP- 1, resulting in reduction of extracellular matrix deposition.