水蛭素对单侧输尿管梗阻大鼠肾间质损伤及MCP-1、ICAM-1的干预效应研究

目的]观察水蛭素对单侧输尿管梗阻（UUO）大鼠肾间质纤维化的干预作用，并探索其作用机制。方法]健康雄性SD大鼠120只，随机分为假手术组24只和造模组96只。造模组再分为模型组24只、水蛭素高剂量组24只、水蛭素低剂量组24只、贝那普利组24只。各组于术后第3、7、14天分批随机处死。取梗阻侧肾组织行逆转录-聚合酶链反应（RT-PCR）、蛋白免疫印迹（Western Blot）分子技术，检测梗阻侧肾组织单核细胞趋化蛋白-1（MCP-1）、细胞间黏附分子-1（ICAM-1）的分子表达变化。结果]苏木精-伊红（HE）染色显示，与模型组相比：各用药组肾间质损伤及纤维化程度均有不同程度改善。RT-PCR显示，与模型组相比：水蛭素高剂量组各时间点及水蛭素低剂量组第7、14天ICAM-1相对表达量均明显降低（P<0.05）；水蛭素高剂量组第7、14天MCP-1表达显著降低（P<0.01）；水蛭素高剂量组第3天及水蛭素低剂量组各时间点MCP-1表达量明显降低（P<0.05）。Western Blot显示，与模型组相比：水蛭素高剂量组第7天ICAM-1蛋白表达量显著减少（P<0.01）；水蛭素高剂量组第3、14天及水蛭素低剂量组第14天各时间点ICAM-1蛋白表达均明显降低（P<0.05）；水蛭素高剂量组第14天MCP-1蛋白表达显著降低（P<0.01）；水蛭素高剂量组第3、7天MCP-1蛋白表达明显降低（P<0.05）。结论]水蛭素能不同程度地改善UUO大鼠肾间质损伤程度，延缓间质纤维化进展，其机制可能与水蛭素干预了UUO大鼠肾间质MCP-1、ICAM-1 mRNA及蛋白质的表达有关。

Study on the effects of hirudin on renal interstitial fibrosis and MCP-1,ICAM-1 in unilateral ureteral obstruction rats

Objective] To observe the effect of hirudin on renal interstitial fibrosis in rats and to explore its mechanism.Methods] The 120 healthy male Sprague-Dawley rats were randomly divided into sham operation group (SOR group) with 24 rats and model group with 96 rats. 96 rats were randomly divided into model group (UUO group) with 24 rats,high-hirudin group (UUO + HI group) with 24 rats,low-hirudin group (UUO + LI group) with 24 rats and benazepril group (UUO + LOT group) with 24 rats. Groups were randomly put to death on 3,7 and 14 days after operation. The obstructed lateral renal tissues were examined by RT-PCR and Western Blot. The molecular expressions of MCP-1 and ICAM-1 were detected.Results] HE staining showed that,compared with the UUO group:the renal interstitial injury and fibrosis in each group were improved to varying degrees. RT-PCR showed that,compared to the UUO group:hirudin high dose group at each time point and hirudin low dose group on day 7,day 14 relative expression of ICAM-1 were significantly decreased (P<0.05);high hirudin dose group on day 7,day 14 of MCP-1 was significantly decreased (P<0.01);hirudin high dose group on day 3 and MCP-1 expression of hirudin low dose group at each time point was significantly decreased (P<0.05). Western Blot showed that compared with UUO group:ICAM 1-protein expression on day 7 hirudin high dose group was significantly reduced (P<0.01);hirudin high dose group on day 3,day 14 and hirudin low dose group day 14 at each time point ICAM-1 protein expression decreased significantly (P<0.05);MCP-1 protein expression on the 14th day hirudin high-dose group was significantly decreased (P<0.01);hirudin high dose group on day 3,MCP-1 expression on day 7 was significantly decreased (P<0.05).Conclusions] Hirudin can improve renal interstitial injury and delay the progress of interstitial fibrosis in rats with UUO to varying degrees,which may be related to the intervention of hirudin in the expression of MCP-1,ICAM-1 mRNA and protein in renal interstitium of UUO rats.