MRL/lpr小鼠血清与尿液中明胶酶活性的增龄变化及意义

目的检测不同周龄MRL/lpr小鼠血清与尿液中明胶酶A（MMP-2）与B（MMP-9）的活性，观察其随增龄的变化及在肾脏病变中的意义。方法留取8、16与24同龄MRL／lpr小鼠的血清、尿液与肾脏组织标本，SDS—PAGE明胶酶谱法检测明胶酶活性，检测不同周龄小鼠尿蛋白含量，并对肾组织进行病理学分级；对尿液中明胶酶的活性与尿蛋白进行相关性分析。结果8，16与24周龄MRL／lpr小鼠血清中仅检测到非活化态MMP-2与MMP-9的活性及微弱的活化态MMP-9，其表达随增龄无明显变化；8周龄小鼠尿液中可以检测到较弱的MMP-2与MMP-9活性，以非活化态为主；16与24周龄小鼠尿液中活化态的MMP-2、MMP-9的表达明显增加，肾组织明胶酶的活性亦随增龄明显增加，变化趋势与尿液相似。尿液中明胶酶的活性与尿蛋白的含量及肾脏组织学改变呈正相关。结论MRL／lpr小鼠尿液中MMP-2、MMP-9活性随增龄明显增加，其活性变化与尿蛋白的发生密切相关，可以反映肾组织增龄性病变程度。

Changes of gelatinases activity in serum and urine of MRL/lpr mice with ageing and its significance

Objective To determine whether increased expressions of gelatinases occur in serum and urine of autoimmune MRL/lpr mice with aging.Methods MRL/lpr mice at the age of 8,16 and 24 weeks were investigated to determine gelatinases activities of serum,urine and kidney specimen by gelatin zymography.Severities of proteinuria and renal pathology were also investigated.Correlation analysis was carried out between urine gelatinase activities and proteinuria levels.Results Pro-enzyme forms of gelatinase A and B as well as active form of gelatinase B were detected in the serum of 8,16 and 24 weeks old mice.No changes were found among groups at different ages.Mild activities of gelatinase A and B mainly in pro-enzyme form could be detected in urine of 8 weeks old mice.In 16 and 24 weeks old mice,increased expressions of both latent and active forms of gelatinase A and B in urine were found,which was similar to the changes found in the kidney specimen.There was positive correlation between the activities of gelatinases and the severities of proteinuria(r=0.51,(P<0.05).)Conclusions Gelatinase A and B expressions in urine were significantly up-regulated with aging in murine lupus nephritis,which might play an important role in development of renal lesions and proteinuria.