摘要
目的:观察水蛭素对单侧输尿管梗阻大鼠肾间质纤维化的干预效应,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、造模组96只,造模组再随机分为:模型组、水蛭素高剂量组、水蛭素低剂量组、贝那普利组,每组24只。各组于术后第3、7、14天分批随机处死。腹主动脉取血,检测Scr、BUN水平;取梗阻侧肾组织行Masson染色,观察肾间质病理损伤程度;Western Blot分子技术检测肾组织PAR-1、NF-κB的蛋白表达变化。结果:各治疗组大鼠血肌酐(Scr)、尿素氮(BUN)水平及肾间质病理损伤程度较模型组均有不同程度改善。与模型组相比,水蛭素高剂量组第3天PAR-1蛋白表达显著降低(P<0.01),贝那普利组各时间点、水蛭素高剂量组第7及14天PAR-1表达明显降低(P<0.05)。水蛭素高剂量组第3及7天、贝那普利组第3天NF-κB表达显著降低(P<0.01);水蛭素高剂量组第14天、水蛭素低剂量组第3天、贝那普利组第7及14天NF-κB表达明显降低(P<0.05)。结论:水蛭素能在一定程度上改善模型大鼠肾间质损伤程度,延缓肾间质纤维化的进展,其作用机制可能与水蛭素干预了模型大鼠肾间质PAR-1、NF-κB蛋白表达有关。
Objective: To observe the intervention effects of Hirudin on the renal interstitial fibrosis in rats with unilateral ureteral obstruction( UUO),and to explore the action mechanism. Methods: 120 SD male rats were randomly divided into the sham-operation group( n = 24),the model group( n = 24),high-dose Hirudin group( n = 24),low-dose Hirudin group( n = 24),and Benazepril group( n = 24). On the 3 rd,7 th,14 th day after the operation,8 rats from each group were randomly sacrificed,blood sample of abdominal aorta were collected for Scr and BUN test; kidney tissue of the obstruction side was taken for observing the damage of renal interstitium with Masson staining; protein expression of PAR-1 and NF-κB of the renal interstitial tissue were detected by Western Blot method. Results: The level of Scr and BUN,and the degree of pathological damage of renal interstitium were improved to varying degrees in all medication groups,compared to the model group. In terms of protein expression of PAR-1,compared to the model group,it was significantly decreased in high-dose Hirudin group on 3 rd day( P < 0. 01),it was obviously decreased as well on 7 th and 14 th day in high-dose Hirudin group and in Benazepril group at each time point( P < 0. 05). In terms of protein expression of NF-κB,it was significantly decreased in high-dose Hirudin group on 3 rd and 7 th day,and in Benazepril group on 3 rd day( P < 0. 01); it was obviously decreased in group high-dose Hirudin group on 14 th day,and in Benazepril group on 7 th and 14 th day( P < 0. 05). Conclusion: Hirudin can improve the damage of renal interstitium and delay the progression of renal interstitial fibrosis in UUO rats,and the mechanism may be related to the intervetion effect of Hirudin on the protein expression of PAR-1 and NF-κB in the renal interstitium.
引文
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