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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 estrogen on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO). Methods Thirty female SD rats were randomly divided into 4 groups: control group I, group II physiological estrogen, group III low estrogen and group IV high estrogen. The rats in each group were sacrificed 21 days after UUO. The histopathological changes in the obstructed kidneys were observed by light microscope. The expressions of α-SMA and metalloproteinases in renal tissues were detected by immunohistochemistry and RT-PCR respectively. 1 tissue inhibitor of (TIMP-1) expression. Results The interstitial fibrosis lesions in the low estrogen group were the most obvious, and the lesions in the high estrogen group were significantly reduced (P <0.01). Compared with physiological estrogen group, the expression of α-SMA and TIMP-1 protein and gene in low estrogen group increased (P <0.05), but decreased in high estrogen group (P <0.05). Conclusion Estrogen may exert renal protective effect by inhibiting the expression of α-SMA and TIMP-1, thereby reducing the deposition of extracellular matrix.