【摘要】 目的　探讨血管紧张素Ⅱ受体拮抗剂氯沙坦对不同时期慢性肾功能衰竭肾小球硬化进程的作用。方法　采用单侧肾摘除加重复静脉注射阿霉素慢性肾功能衰竭大鼠模型 ,将动物分为正常对照组 (N组 )、慢性肾衰疾病组 (D组 )、氯沙坦早期治疗组 (ET组 )及氯沙坦晚期治疗组(LT组 )。检测各组大鼠的血尿素氮 (BUN)、血肌酐 (Scr)、2 4小时尿蛋白排泄率 (TP/2 4h)、平均动脉压 (MAP)以及肾小球平均截面积和平均体积。采用免疫组织化学方法检测肾组织内转化生长因子 β(TGF β)和细胞外基质成分纤维连接蛋白 (FN )的表达。 结果　ET组大鼠BUN、Scr、TP/2 4h、MAP以及肾小球平均截面积和平均体积均显著低于D组和LT组 (P <0 .0 5 ) ,肾组织TGF β和FN表达明显减少 ;LT组各项生化指标水平、MAP、TGF β和FN表达较D组明显下降 (P <0 .0 5 ) ,但程度远不如ET组显著 ;肾小球平均截面积和平均体积虽较D组有所下降 ,但差异无显著性。结论　早期给予氯沙坦治疗能有效抑制TGF β表达 ,延缓慢性肾衰肾小球硬化的进程 ,晚期氯沙坦治疗也能一定程度地改善肾脏组织形态学改变 ,但效果远不如早期治疗更多还原

【Abstract】 Objective To explore the effects of early and late losartan treatment on the development and progression of glomerulosclerosis in chronic renal failure.Method Experimental chronic renal failure in rats was induced by uninephrectomy with intravenous adriamycin injection.The following groups of rats were employed: normal control group(N group),chronic renal failure group (D group),early losartan treatment group (ET group) and late losartan treatment group (LT group).Plasma nitrogen and creatinine,urinary protein excretion and mean arterial pressure (MAP) as well as the glomerulosclerosis profile of the average areas (AG) and volumes (VG) of the glomeruli were measured.Transforming growth factor-β(TGF-β) and fibronectin (FN) expression were examined by immunohistochemistry method.Results Plasma nitrogen and creatinine, urinary protein excretion,MAP and the AG and VG in ET group were significantly lower than those in D group and LT group (P<0.05).TGF-β and FN expression decreased significantly in ET group.There was no significant difference in AG and VG between LT group and D group.TGF-β,FN,plasma nitrogen,creatinine,urinary protein and MAP in LT group were lower than those in D group (P<0.05).Conclusion Both early and late losartan treatment prevent the development and progression of glomerulosclerosis in chronic renal failure rats, but late treatment is not so beneficial as early treatment to improve renal function and renal histopathology.更多还原