双环醇对单侧输尿管梗阻大鼠肾间质PAI-1表达的影响

Effects of bicyclol on renal PAI-1 expression in rats with uniliteral ureteral obstruction

目的探讨双环醇延缓肾间质纤维化的可能机制。方法将81只Sprague-Dawley(SD)大鼠随机分为假手术组,模型组和治疗组3组。采用单侧输尿管梗阻(UUO)致肾间质纤维化大鼠模型,治疗组在制模后给予双环醇灌胃治疗。7、14、21 d取梗阻侧肾组织行苏木精-伊红及Masson染色,观察肾脏病理学变化。免疫组化法检测肾组织纤溶酶原激活物抑制-1(PAI-1)的表达。RT-PCR法检测肾组织PAI-1 mRNA的表达水平。结果治疗组7 d、14 d、21 d肾间质纤维化的相对面积分别为(9.6±0.6)%、(16.8±0.8)%、(33.6±1.6)%,较模型组[分别为(13.0±0.7)%、(25.8±1.5)%、(53.2±2.5)%]明显降低(均P<0.05);同时治疗组肾组织PAI-1蛋白表达及PAI-1 mRNA的表达均较模型组减少(均P<0.05)。结论双环醇能够减轻UUO所致的肾间质损伤及纤维化程度,其作用机制可能是通过下调PAI-1的表达从而延缓肾间质纤维化的进程,发挥对肾脏的保护作用。

Objective To explore the protective effects of bicyclol against renal interstitial fibrosis and possible mechanisms of the protection.Methods Eighty-one Sprague-Dawley（SD） rats were randomly assigned to a sham-operated group and UUO groups with and without bicyclol treatment.A rat model of renal interstitial fibrosis was prepared by unilateral ureteral obstruction（UUO）.Renal tissues were examined by hematoxylin eosin and Masson staining on 7,14 and 21 days.Immunhistochemistry was used for determining plasminogen activator inhibitor-1（PAI-1） expression in the renal interstitium.PAI-1 mRNA expression in renal tissues was semi-quantitatively determined by reverse transcription-polymerase chain reaction（RT-PCR）.Results The relative areas of renal interstitial fibrosis in the bicyclol-treated UUO group 7,14 and 21days after operation were（9.6±0.6）%,（16.8±0.8）% and（33.6±1.6）% respectively,which were significantly lower than those in the untreated UUO group [（13.0±0.7）%,（25.8±1.5）% and（53.2±2.5）% respectively]（P〈0.05）.The levels of protein and mRNA expression of PAI-1 in the bicyclol-treated UUO group decreased significantly compared with those in the untreated UUO group 7,14 and 21days after operation（P〈0.05）.Conclusions Bicyclol can alleviate renal interstitial injury and renal interstitial fibrosis caused by UUO in rats,possibly through a down-regulation of renal PAI-1 expression.