双环醇对单侧输尿管梗阻大鼠肾间质纤维化的影响及其机制

摘要

目的 通过双环醇干预单侧输尿管梗阻(UUO)模型大鼠,动态观察核转录因子-κB(NF-κB)、细胞间黏附因子-1(ICAM-1)在梗阻侧肾间质中的表达,探讨双环醇延缓肾间质纤维化(RIF)的机制.方法 建立 UUO致肾间质纤维化大鼠模型,将81只大鼠随机分为假手术组、模型组、治疗组.治疗组于术后第1天开始给予双环醇200 mg/kg灌胃;假手术组和模型组给予等量生理盐水灌胃.在术后第7、14、21天每组各取9只处死,取动脉血分离血清测血肌酐和血尿素氮,观察大鼠肾功能变化.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.用免疫组化方法检测肾组织NF-κB 、ICAM-1表达.结果 治疗组血清肌酐和尿素氮较模型组显著下降,差异有统计学意义(P ＜ 0.01).治疗组肾小管间质损伤评分和RIF相对面积均低于模型组(P均＜ 0.05).治疗组肾组织的NF-κB、ICAM-1蛋白表达显著低于模型组(P均＜ 0.05).结论 双环醇能够减轻UUO所致的肾间质损伤及RIF程度,其作用机制可能177(11):7485-7496.%Objective To observe the expression of nuclear factor-κB (NF-κB) , intercellular adhesion molecule-1 (ICAM-1) in the renal interstitum in rats with unilateral ureteral obstruction (UUO), to explore the renoprotective effect of bicyclol and its mechanism.Methods Renal interstitial fibrosis was produced by unilateral ureteral obstruction in rats.Eighty-one rats were randomly assigned to sham operation group, UUO model group and bicyclol-treated group.After operations rats in bicyclol-treated group were intragastrically administered with bicyclol at 200 mg/kg once a day until rats were killed.Rats in sham-operated group and UUO model group were administrated at identical valuminal normal saline.In each group, nine rats were chosen randomly to be killed at the 7 d, 14 d and 21 d after operation for histological examination of kidney tissue.Renal tissues were examined by hematoxylin-eosin staining and Masson staining, Immunhistochemistry was performed on NF-κB expression in the renal interstitum.Results The renal damage (serum creatinine and blood urea nitrogen) in bicyclol treatment group is better than that in UUO model group at day 21 (P ＜ 0.01 ).Compared with UUO model group, the score of renal interstitial damage and fibrotic area in bicyclol-treated group were decreased markedly at three time points (P ＜ 0.05, respectively).The expression of NFκB and ICAM-1 in bicyclol-treated group was decreased markedly at three time points (P ＜ 0.05, respectively).Conclusions Bicyclol can alleviate the degree of renal interstitial fibrosis and protect renal function through decreasing the expression of NF-κB and ICAM-1, thus blocking the renal fibrosis.