MMP-9、TIMP-1在阿霉素肾病大鼠肾小管间质病变中的表达

目的 :研究 MMP- 9及 TIMP- 1在大鼠阿霉素肾病肾小管间质病变中的表达变化及意义。方法 :采用大鼠尾静脉单剂量注射阿霉素 7.5 mg/kg建立阿霉素肾病模型 ,雄性 Wistar大鼠 64只 ,分为正常对照组、阿霉素肾病组。于 7、 1 4、2 8、5 6d四个时间点依次各处死 8只大鼠留取标本。光镜下观察肾小管间质形态学改变 ,生物化学方法检测血清肌酐、胆固醇、白蛋白 ,2 4 h尿蛋白定量 ,免疫组织化学检测肾组织 MMP- 9、TIMP- 1、 型胶原的表达。结果 :阿霉素肾病组大鼠肾小管间质损害明显 ,肾小管上皮细胞 MMP- 9的表达明显上调 ,于第 1 4天达高峰。肾小管的 TIMP- 1的表达上调 ,第 2 8、5 6天与同期对照组相比差异显著。肾小管上皮细胞 TIMP- 1的表达与肾组织 型胶原表达呈正相关 ;MMP- 9/TIMP- 1比值 型胶原表达呈负相关。结论 :阿霉素肾病组大鼠肾小管 MMP- 9、TIMP- 1的表达上调 ,MMP- 9/TIMP- 1的失衡可能参与肾小管间质纤维化的发生发展过程

The expression of MMP-9 and TIMP-1 on renal tubulointerstitial in rats with adriamycin-induced nephropathy

Objective:To investigate the expression feature and the significance of MMP-9 and TIMP-1 on renal tubulointerstitial in rats with adriamycin-induced nephropathy. Method: The model was established in rats by tail vein injection of adriamycin 7.5mg/kg. The samples were studied 7,14,28 and 56 days later.Renal histopathological changes ,serum creatinine and cholesterol , urine protein excretion were measured; the expressions of protein of collagen Ⅳand MMP-9、TIMP-1 in the cortex of the kidney were examined utilizing immunohistochemistry. Results: We have successfully established ADR nephropathy model. It was shown that in the tubulointerstitial injury, collagen Ⅳ protein and the excretion of urine protein in nephrotic rats were significantly increased as compared with those of the normal control group. In nephropathy group the expression of MMP-9 in the tubular cells increased at 7 day,and reached the peak at 14 day,The quantities were significantly higher than normal group.The expression of TIMP-1 increased significantly as compared to the normal group at 14,28,and 56 days. The expression of TIMP-1 and MMP-9/ TIMP-1were significantly correlated to the collagen Ⅳ protein. Conclusions: The inequality between MMP-9 and TIMP-1 contributed to the pathogenesis of tubulointerstitial fibrosis.