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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 investigate the expression of TIMP-1 in renal tubulointerstitium and its relationship with tubulointerstitial injury in unilateral ureteral obstruction (UUO) rats. Methods UUO rat model was established. The expression of TIMP-1, α-smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA) in the tubulointerstitium were detected by immunohistochemistry on the 1st, PCNA) and monocyte-macrophage antigens (ED) -1 and its relationship with tubulointerstitial damage after ureteral obstruction. Results A small amount of TIMP-1-expressing cells were found in the renal interstitium on the first day after UUO. TIMP-1 expression was significantly increased in the third to seventh days after UUO, which was mainly expressed in renal tubular epithelial cells and renal interstitium. On the third day after UUO, the expression of PCNA reached the peak, then decreased, but the level of PCNA in renal interstitium was still higher on the 7th to 14th day. On the third day after UUO, α-SMA expression was detected in renal interstitial fibroblasts and renal tubular epithelial cells and increased with time. The positive area of α-SMA was positively correlated with the relative area of renal interstitium (r = 0.924, p <0.01). The expression of TIMP-1 was positively correlated with the relative area of interstitial (r = 0.835, P <0.05) and α-SMA positive area (r = 0.922, P <0.01). Conclusions TIMP-1 protein is expressed early in tubulointerstitial lesion and earlier than interstitial fibrosis in renal tubulointerstitial lesions. The expression of TIMP-1 protein is positively correlated with the expression of α-SMA and the relative area of renal interstitium, Progress is gradually increasing. The high expression of TIMP-1 in renal tubular epithelial cells and interstitial cells and the proliferation of renal tubular epithelial cells and interstitial cells may be involved in the mediation of tubulointerstitial damage after UUO.