组织型纤溶酶原激活物、尿激酶型纤溶酶原激活物在单侧输尿管梗阻大鼠不同阶段肾组织中的表达及意义

Expression and significance of tissue plasminogen activator and urokinase plasminogen activator in the renal tissue of unilateral ureteral obstructive rats at different stages

目的:建立单侧输尿管梗阻大鼠模型,观察组织型纤溶酶原激活物(t-PA)、尿激酶型纤溶酶原激活物(u-PA)在不同时间点肾组织中的表达情况,探讨其不同的表达与肾间质纤维化的关系。方法:实验于2006-05/2007-04在泸州医学院附属医院病理学实验室及传染免疫学实验室完成。72只清洁级雄性SD大鼠,随机分为3组,正常组24只,假手术组24只,模型组24只。各组大鼠于单侧输尿管结扎术后1,4,7,14d取肾组织进行病理分析,观察各组大鼠于单侧输尿管梗阻术后1,4,7,14d的肾小管损伤与肾间质纤维化情况,并采用免疫组织化学技术动态观察t-PA、u-PA在各组的表达情况。实验过程中对动物处置符合动物伦理学标准。结果:参加实验动物72只,中途共死亡5只,均及时补充,最后进入结果分析大鼠为72只。①模型组术后4d,肾脏组织即表现早期纤维化的病理改变,术后第7天,肾小管表现出明显损害,术后14d,肾间质纤维化表现明显。②假手术组较正常组各时间点t-PA、u-PA表达明显减少(P<0.05),模型组t-PA、u-PA在梗阻初期均随梗阻时间延长表达增多,术后第4天表达最多,以后随梗阻时间延长表达逐渐减少。结论:在输尿管梗阻早期,肾组织可能自身代偿分泌合成t-PA、u-PA,在一定程度下有利于延缓肾间质纤维化的进展,随着纤维化的发展,肾小管上皮细胞变性坏死,t-PA、u-PA分泌逐渐减少。

AIM： To establish rat models of unilateral urateral obstruction （UUO）, and observe the expression of tissue plasminogen activator （t-PA） and urokinase plasminogen activator （u-PA） in renal tissue at different stages so as to explore the correlation between the expression and renal interstitial fibrosis. METHODS： The experiment was carried out in the pathology laboratory and infection immunity laboratory of Affiliated Hospital of Luzhou Medical College from May 2006 to April 2007. Seventy-two clean-grede male SD rats were randomly divided into normal group, sham operation group and model group with 24 animals in each group. The renal tissue was harvested for pathological analysis at 1, 4, 7 and 14 days after UUO. The renal tubule damage and renal interstitium fibrosis circumstance of each rat were observed on days 1, 4, 7 and 14 after UUO, and the immunohistochemical technique was used to dynamically observe the expression of t-PA and u-PA in 3 groups. All the treatments for animals were accorded to the ethical standards. RESULTS： Seventy-two animals were enrolled and 5 died during experiment but supplemented in time. Finally, 72 rats were involved in the result analysis. （1）After 4 days of UUO, renal tissue presented earlier period pathological change of fibrosis in model group; After 7 days, nephric tubule appeared obviously damage; After 14 days, obvious renal interstitial fibrosis was found. （2）The expression of t-PA and u-PA in sham operation group was obviously decreased compared with normal group at each time point of UUO （P 〈 0.05）; the expression of t-PA and u-PA in the initiat stage of obstruction gradually increased as days prolonging in model group, and reached the maximum on day 4 of UUO, then decreased gradually. CONCLUSION： In the initial stage of UUO, renal tissue maybe compensatory excrete and synthesize t-PA and u-PA by themselves, which is profit to delay the advancement.of renal interstitial fibrosis more or less; with the development of fibrosis, renal tubular epithelial cell degeneration and necrosis are found, and the secretion of t-PA and u-PA is decreased gradually.