金属蛋白酶组织抑制剂1在大鼠肾小管间质损害中的表达及其意义  

Role of TIMP-1 expression in renal tubulointerstital lesion induced by unilateral ureteral obstruction

作　　者：董健平[1] 陈香美[1] 师锁柱[1] 田月[1] 

机构地区：[1]解放军总医院肾内科解放军肾脏病重点实验室,北京100853

出　　处：《中华肾脏病杂志》2002年第4期275-279,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金(30000080);国家重点基础研究发展规划项目(G2000057003)

摘　　要：目的 观察单侧输尿管梗阻(UUO)大鼠模型中金属蛋白酶组织抑制剂1(TIMP-1)在肾小管间质中的表达部位、动态变化及其与肾小管问质损害的关系。方法 制备UUO大鼠模型,采用免疫组织化学方法检测UUO术后第1、3、5、7、14天肾小管间质中TIMP-1、α-平滑肌肌动蛋白(SMA)、增殖细胞核抗原(PCNA)和单核巨噬细胞抗原(ED)-1的表达及其与输尿管梗阻后肾小管间质损害的关系。结果 UUO术后第1天肾间质可见少量TIMP-1表达细胞,第3～7天TIMP-1表达明显增加,主要表达于肾小管上皮细胞和肾间质。UUO术后第3天肾小管PCNA表达达高峰,随后下降,而肾间质PCNA水平于第7～14天仍较高。UUO术后第3天肾间质成纤维细胞及肾小管上皮细胞可检出α-SMA表达并随时间递增。α-SMA阳性面积与肾间质相对面积成正相关(r=0.924,p<0.01)。TIMP-1表达与间质相对面积(r=0.835,P<0.05)及α-SMA阳性面积(r=0.922,P<0.01)成正相关。结论 TIMP-1蛋白质于肾小管间质病变早期表达于肾小管间质,早于肾间质纤维化出现,其表达量与肾间质α-SMA表达及肾间质相对面积呈正相关并随病变进展逐渐增加。TIMP-1在肾小管上皮细胞和问质细胞的高表达及肾小管上皮细胞和间质细胞增殖可能参与介导UUO术后肾小管间质损害。Objective To explore the role of tissue inhibitor of metalloproteinase-1 (TIMP-1 )in the renal tubulointerstitial lesions induced by unilateral ureteral obstruction (UUO) . Methods Rats were sacrificed at 1, 3, 5, 7 and 14 days after UUO or sham-surgery. The protein expression of TIMP-1 ,α-smooth muscle actin(α-SMA) .proliferating cell nucleus antigen (PCNA) and ED-1 in tubulointerstitium were detected by immunohistochemistry at each time point. Rusults TIMP-1 expression in renal tubulointerstitium increased progressively starting from 24 hours to day 14 post-ligation. TIMP-1 was mainly expressed in interstitial and some tubular cells. On 24 hours post-ligation a few α-SMA-positive interstitial cells and ED-1-positive macrophages were present. From day 3 the number of a-SMA-positive interstitial cells and ED-1-positive macrophages increased. Some tubular epithelial cells also expressed α-SMA. The renal tubulointersital expression of TIMP-1 was significantly associated with the relative volume of interstitium and the postive area of α-SMA. The expression of PCNA in tubular cells peaked at day 3 after UUO, then decreased, but there were still many PCNA-positive interstitial cells at day 7 and day 14. Conclusion TIMP-1 is active in interstitial and tubular cells in the early phase of fibrotic process and may play an important role in mediating the tubulointerstital lesions after UUO.

关 键 词：大鼠 金属蛋白酶组织抑制剂1 输尿管梗阻 纤维化 肾小管间质损害 免疫组织化学 细胞增殖 

分 类 号：R692.6[医药卫生—泌尿科学]