纤溶系统对膜性肾病大鼠足细胞损伤的影响  

Effect of fibrinolytic system on the podocyte injury in rats with membranous nephropathy

作　　者：梁静[1] 张渊[2] 曹灵[3] 孟祥龙[1] 王莉[2] 

机构地区：[1]四川省医学科学院.四川省人民医院城东病区肾脏科,成都610110 [2]四川省医学科学院.四川省人民医院肾脏科,成都610072 [3]泸州医学院附属医院肾病内科,四川泸州646000

出　　处：《中国实验动物学报》2016年第3期283-287,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：四川省卫生厅科研课题(编号:110238)

摘　　要：目的探讨早期预防纤溶紊乱对防止MN进展有重要意义。方法按改良Border法制作MN大鼠模型,正式免疫第1、2、3、4周末检测全血uPA、tPA及PAI-1的表达水平;取大鼠肾组织进行光镜、电镜观察肾组织病理学改变;采用免疫组化方法检测肾足细胞nephrin、WTl蛋白表达含量,并进行相关性分析。结果与正常组及干预组大鼠相比,模型组大鼠的全血uPA、tPA水平明显减少,而PAI-1水平明显增加,差异具有统计学意义(P<0.05);电镜显示肾小球足细胞广泛足突融合至消失;GBM基质出现"钉样突起",肾间质纤维化程度较重。肾小球足细胞分布区WT-1和nephrin蛋白表达下调,其中nephrin蛋白表达量变化有统计学意义(P<0.01)。相关性分析显示,大鼠全血tPA和uPA水平与肾组织nephrin蛋白的表达变化呈正相关,全血PAI-1水平与肾组织nephrin蛋白的表达变化呈现负相关。结论在MN发展中,纤溶系统对足细胞损伤凋亡具有重要意义,早期评估预测MN足细胞损伤情况或可为防治早期MN步入终末期肾脏病找到又一治疗靶点,亦可为临床研究治疗MN的药物提供新的思路。Objective To observe the expression of uPA,tPA and PAI-1 in whole blood of rat membranous nephropathy（ MN） models induced by cationic bovine serum albumin（ C-BSA）,and to explore the effect of fibrinolytic system on podocyte apoptosis and pathological changes. To explore the possible preventive and therapeutic effects and the possible mechanisms of early prevention of fibrinolysis. Methods We developed a MN model with the modified Border method. At the end of the 1st,2nd,3th,and 4th week of immunization,respectively,the levels of whole blood uPA,tPA and PAI-1 were determined by ELISA. The rat kidney tissues were examined by light microscopy and electron microscopy to identify the pathological changes. The expression levels of nephrin and WTl were detected with immumofluorescence staining and their correlation was analyzed. Results Compared the treatment group with control group,the levels of whole blood uPA,tPA and PAI-1 of the model group were decreased,while PAI-1 was elevated,showing a significant difference（ P〈0. 05）. The degree of renal interstitial fibrosis was more serious. Correlation analysis showed that the whole blood tPA and uPA levels were positively correlated with the changes of nephrin protein expression in the kidney tissue,while the whole blood PAI-1 level was negatively correlated with the nephrin protein expression in the kidney tissue. Conclusions In the process of MN development,the fibrinolytic system may have important significance for podocyte apoptosis. Determination of early phase of MN podocyte injury may be another therapy target for prevention of the disease development,and then provide new ideas for clinical research and drug development for MN.

关 键 词：膜性肾病 足细胞 NEPHRIN WT-1 纤溶系统 

分 类 号：Q95-33[生物学—动物学]