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

摘要:

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。

Abstract:

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.