氯沙坦对进展性肾炎模型大鼠肾小管-间质细胞巨噬细胞移动抑制因子的影响研究

Effects of Losartan on MIF in Tubulointerstitial Cells in Progressive Nephritis Model Rats

目的:探讨氯沙坦对进展性肾炎模型大鼠肾小管-间质细胞巨噬细胞移动抑制因子(MIF)的影响。方法:取大鼠行右肾切除并注射鼠单克隆IgG(OX-7)抗Thy1.1抗体2次建立进展性肾炎大鼠模型,于第4周时取部分大鼠立即处死作为模型组,将剩余模型大鼠分为对照组和氯沙坦高、低剂量组(80、20mg.kg-1.d-1),再另取大鼠行假手术作为假手术组,每组5只,各组灌胃给予相应药物连续4周,观察各组大鼠肾小管-间质细胞中MIF、巨噬细胞标记抗原ED-1的表达及肾组织病理变化。结果:与假手术组比较,模型组大鼠肾小管-间质细胞中MIF、ED-1表达明显升高(P<0.001);与对照组比较,氯沙坦高、低剂量组MIF、ED-1表达明显降低(P<0.01或P<0.001)。病理观察发现,模型组大鼠肾小管-间质受损,而氯沙坦高、低剂量组肾小管-间质的损伤均有改善。结论:氯沙坦可能通过降低进展性肾炎模型大鼠MIF和ED-1的表达来发挥抑制肾小管-间质细胞炎症反应的作用。

OBJECTIVE： To investigate the effects of losartan on macrophage migration inhibitory factor （MIF） in tubulointerstitial cells in progressive nephritis model rats. METHODS： Rats were selected and underwent right nephrectomy and injected IgG （OX-7） mouse monoclonal anti-Thy1.1 antibody twice, and progressive nephritis model was established. Some rats were sacrificed at 4th week as model group, and other rats were divided into control group and losartan high-dose and low-dose groups （80, 20 mg.kg-1.d-1） with 5 rats in each group. Other rats were selected as sham operation group. Relevant drugs were irrigated into the stomachs of the rats for 4 weeks in all groups. The expression of MIF and macrophage marker antigen ED-1, and the tubulointersti- tial pathological changes were examined. RESULTS： Compared with sham operation group, the expression of MIF and ED-1 in- creased significantly in model group （P〈0.001）; compared with control group, the expression of MIF and ED-1 decreased significantly in losartan high-dose and low-dose groups （P〈0.01 or P〈0.001）. Pathological observation indicated that tubulointerstitial injury was found in model group, and tubulointerstitial injury was ameliorated in losartan high-dose and low-dose groups. CONCLUSION： Losartan may ameliorate the progression of tubulointerstitial inflammation by intervene the expression of MIF and ED-1 in the progressive nephritis model rat.