基质金属蛋白酶-2和金属蛋白酶抑制物-1在抗体介导的慢性排斥反应患者肾组织中的表达及意义

摘要

目的 研究移植肾组织中基质金属蛋白酶(MMP-2)和金属蛋白酶抑制物-1(TIMP-1)表达和抗体介导的慢性排斥反应的关系.方法 用免疫组织化学技术和计算机真彩色图像分析系统半定量检测46例抗体介导的慢性排斥反应患者移植肾组织中MMP-2和TIMP-1的表达情况,分析二者与肾功能关系及与ABMR的间质纤维化与肾小管萎缩(IF/TA)的病理分级之间的关系.15例正常肾组织作为对照.结果 慢性排斥反应移植肾组织中MMP-2和TIMP-1的表达比正常肾组织明显增加(P＜0.05),MMP-2的表达随IF/TA病理分级增加呈递减趋势(各组间比较P＜0.05),TIMP-1的表达随IF/TA病理分级增加呈递增趋势(各组间比较P＜0.05)；随着纤维化程度的加重,患者肾功能血肌酐逐渐上升(P＜0.05); TIMP-1的表达与血肌酐正相关(r=0.718,P＜0.05).结论 本研究结果显示MMP-2和TIMP-1异常表达促进着移植肾纤维化的发展.%Objective To investigate the expressions of matrix metalloprotein-2 (MMP-2) and tissue inhibitor of metallopeptidase inhibitor-1 (TIMP-1) in the renal allografts of patients with chronic active antibody-mediated rejection (ABMR), and explore their role in the pathogenesis of ABMR. Methods Immunohistochemistry and computer-assisted image analysis were used to detect the expression of MMP-2 and TIMP-1 in the renal allografts of 46 patients with interstitial fibrosis and tubular atrophy (IF/TA), with 15 normal renal tissue specimens as the control. The association of MMP-2 and TIMP-1 with the pathological grade of IF/TA in ABMR was analyzed. Results The expressions of MMP-2 and TIMP-1 significantly increased in the renal tissues of the patients as compared with the normal renal tissues (P<0.05). MMP-2 expression tended to decrease, while TIMP-1 and serum creatinine increased with the pathological grades of IF/TA (P<0.05). In IF/TA group, the expression of TIMP-1 was positively correlated to serum creatinine level (r=0.718, P=0.00<0.05). Conclusions Abnormal expressions of MMP-2 and TIMP-1 can promote the development of renal fibrosis in chronic ABMR.