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乌司他丁通过转化生长因子 β(TGF-β)/Smad 信号通路抑制单侧输尿管梗阻诱导的大鼠肾间质纤维化。

Ulinastatin inhibits unilateral ureteral obstruction-induced renal interstitial fibrosis in rats via transforming growth factor β (TGF-β)/Smad signalling pathways.

机构信息

Second Affiliated Hospital Harbin Medical University, Harbin 150086, China.

出版信息

Int Immunopharmacol. 2013 Feb;15(2):406-13. doi: 10.1016/j.intimp.2012.12.019. Epub 2013 Jan 11.

DOI:10.1016/j.intimp.2012.12.019
PMID:23318600
Abstract

This study aims to explore the protective effects and mechanisms of ulinastatin (UTI), which is a urinary trypsin inhibitor, of the renal interstitial fibrosis of rats subjected to unilateral ureteral obstruction (UUO). A total of 36 male Wistar rats were divided in random into three groups, namely, the sham operation (SOR) group (n=12), the UUO group (n=12), and the UTI treatment group (n=12). Six rats from each group were euthanised after unilateral ureteral obstruction operation on the seventh and fourteenth days, respectively. Blood samples were harvested for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement. The interstitial pathological changes of the tissue from the obstructed kidneys were observed using haematoxylin-eosin (H&E) and Masson staining. The expression of the transforming growth factor β type 1 (TGF-β1), α-smooth muscle actin (α-SMA), type I collagen (Col-I), and phosphorylated Smad2/3 (p-Smad2/3) was determined using immunohistochemistry. The protein expression levels of TGF-β1, α-SMA, and p-Smad2/3 were examined using Western blot analysis. The results show that ulinastatin has no statistically significant effect on the BUN and Scr levels (P>0.05), but it can significantly reduce renal interstitial injury and suppress interstitial collagen deposits. The renoprotective effect of ulinastatin is likely realised through the TGF-β/Smad signalling pathways.

摘要

本研究旨在探讨尿胰蛋白酶抑制剂乌司他丁(UTI)对单侧输尿管梗阻(UUO)大鼠肾间质纤维化的保护作用及其机制。36 只雄性 Wistar 大鼠随机分为假手术(SOR)组(n=12)、UUO 组(n=12)和 UTI 治疗组(n=12)。每组各有 6 只大鼠分别在单侧输尿管梗阻术后第 7 天和第 14 天处死。采集血液样本测定血尿素氮(BUN)和血清肌酐(Scr)。采用苏木精-伊红(H&E)和 Masson 染色观察组织的间质病理变化。采用免疫组织化学法检测转化生长因子β 型 1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)、I 型胶原(Col-I)和磷酸化 Smad2/3(p-Smad2/3)的表达。采用 Western blot 分析检测 TGF-β1、α-SMA 和 p-Smad2/3 的蛋白表达水平。结果表明,乌司他丁对 BUN 和 Scr 水平无统计学意义(P>0.05),但能明显减轻肾间质损伤,抑制间质胶原沉积。乌司他丁的肾保护作用可能通过 TGF-β/Smad 信号通路实现。

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