氯沙坦减轻梗阻性肾病大鼠肾间质纤维化及肾小管上皮细胞凋亡机制的研究

Mechanism of Losartan on Renal Interstitial Fibrosis and Renal Tubular Epithelial Cell Apoptosis in Rats with Obstructive Nephropathy

目的探讨氯沙坦对单侧输尿管梗阻大鼠模型肾小管上皮细胞凋亡和肾间质纤维化的影响及其可能机制。方法通过结扎并离断大鼠单侧输尿管制作梗阻性肾病模型,对照组进行假手术。留取术后第3,5,7及14天肾脏组织及血尿标本。结果单侧输尿管梗阻使α-SMA和Ⅰ型胶原蛋白的表达水平明显增加,并导致肾小管间质纤维化和肾组织细胞凋亡明显增加。肾间质纤维化的进展伴随着STAT3的磷酸化和2种凋亡相关蛋白(Bax和Bcl-2)的表达改变。氯沙坦干预治疗可以减少这些变化。结论在单侧输尿管梗阻的大鼠模型中,氯沙坦能缓解肾脏纤维化及肾小管细胞的凋亡程度。这种疗效可能是通过部分阻滞STAT3信号通路完成的。

Objective To investigate the effects of losartan on renal tubular cell apoptosis and renal fibrosis in a rat model of UUO, and explore the related mechanism. Methods Rats were subjected to UUO by ureteral ligation and treated with dimethyl sulfoxide （control） or losartan. Controls were given sham operations. Renal tissues were collected 3,5,7, and 14 days after surgery for measurement of various indicators of renal fibrosis. Resuits UUO increased the expression of α-SMA and collagen Ⅰ , and improved the extent of renal tubular fibrosis and apoptosis in a time-dependent manner. Losartan treatment partially reversed these effects. Progression of renal interstitial fibrosis was accompanied by phosphorylation of signal transducer and activator of transcription 3 （STAT3） and altered expression of two-apoptosis-related proteins （Bax and Bcl-2）. Losartan treatment also partially reversed these effects. Conclusion Our results indicate that losartan attenuates renal fibrosis and renal tubular cell apoptosis in a rat model of UUO. This effect appears to be mediated by partial blockage of STAT3 phosphorylation.