肾小管间质纤维化大鼠基质金属蛋白酶-9/金属蛋白酶组织抑制因子-1的表达

目的 观察肾小管间质纤维化（TIF）大鼠基质金属蛋白酶-9（MMP-9）、金属蛋白酶组织抑制因子-1（TIMP-1）的表达，探讨MMP-9、TIMP-1在11F中的作用。方法 选用SD大鼠48只。随机分为假手术组和模型组，制备单侧输尿管梗阻（UUO）模型。采用病理及免疫组织化学等方法动态观察组大鼠d7、d14、d21梗阻侧肾脏的组织学变化和MMP-9、TIMP-1在梗阻肾小管间质中表达情况。结果 各时间点假手术组TIMP-1表达量低于模型组（Pa〈0．01），MMP-9／TIMP-1表达量比值均高于模型组（P。〈0．01）。各时间点肾小管间质损害与TIMP-1表达量呈正相关（r=0．901P〈0．01），与MMP-9／TIMP-1比值呈负相关（r=-0．937 P〈0．01）。结论 TIMP-1可能是肾间质纤维化形成促进因素之一，并参与纤维化形成的全过程。MMP-9／TIMP-1失衡参与TIF的发生机制。

Expression of Matrix Metalloproteinase-9/Tissue Inhibitor of Metalloproteinase-1 in Rats with Tubulointerstitial Fibrosis

Objective To observe the expression of matrix metalloproteinase-9(MMP-9)/tissue inhibitor of metalloproteinase-1(TIMP-1) in tubulointerstitial fibrosis(TIF) rats and explore the effects of MMP-9 and TIMP-1 in TIF.Methods Forty-eight male Sprague-Dawley(SD) rats were randomly divided into sham-operated group(n=24) and model group(n=24).Results Tubulointerstitial fibrosis model was established via unilateral ureteral obstruction(UUO). Histological changes were observed in tubulointerstitium injury under microscope and immunohistochemistry staining was performed to investigate both the expression of MMP-9 and TIMP-1 in TIF by semiquantitative score at d7, d14, d21 after experiment onset.The expressions of TIMP-1 in rats from sham-operated group were lower than those of mo-del group rats at d7, d14, d21 (Pa<0.01). The relative values of MMP-9/TIMP-1 in rats from sham-operated group were higher than those of model group rats at d7,d14, d21(Pa<0.01). There was positive correlation between renal interstitial injury and TIMP-1 expression(r=0.901 P<0.01) and negative correlation between renal interstitial injury and the relative value of MMP-9/TIMP-1(r=-0.937 P<0.01).Conclusions The unbalance between the expression of MMP-9 and TIMP-1 may promote the progress of TIF. TIMP-1 may be a key factor in aggravating TIF and plays an important role in the process of TIF.