纤维蛋白诱导活化系膜细胞表达明胶酶A、B的机制研究  

STUDY ON MECHANISMS UNDERLYING THE INDUCTION AND ACTIVATION OF GELATINASE A AND B IN CULTURED HUMAN GLOMELULAR MESANGIAL CELLS INDUCED BY FIBRIN

作　　者：蔡广研[1] 陈香美[1] 傅博[1] 吕扬[1] 

机构地区：[1]解放军总医院,北京100853

出　　处：《解放军医学杂志》2001年第12期877-879,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础研究发展规划 973项目资助课题 (编号G2 0 0 0 0 570 0 3)

摘　　要：为观察纤维蛋白对系膜细胞 (HMC)表达明胶酶A(MMP 2 )、明胶酶B(MMP 9)的作用并探讨其活化机制 ,应用RT PCR、明胶酶谱分析法分别在基因转录水平与蛋白质活性水平上检测纤维蛋白对HMC表达MMP 2、MMP 9的作用 ,采用纤维蛋白酶谱法与平板法检测纤维蛋白对HMC表达纤溶酶原激活物 (PA)活性的影响。结果发现 ,纤维蛋白呈剂量与时间依赖性促进HMCMMP 2与MMP 9表达的上调 ,并同时促进HMCtPA与uPA的表达 ;应用抑肽酶阻断纤溶酶活性后能够完全阻断 pro MMP 2与pro MMP 9的活化。提示肾脏局部沉积的纤维蛋白可以促进HMC表达与活化MMP 2、MMP 9,而MMP 2与MMP 9的活化依赖于PA/纤溶酶系统的调控。To investigate the effects of covering fibrin on the expression of gelatinase A and gelatinase B in cultured human glomerular mesangial cells (HMC) and the mechanism undarlying the activation of gelatinase A and gelatinase B. RT-PCR and gelatin zymography were used to detect the changes in gelatinase A(MMP-2) and gelatinase B(MMP-9) in HMC at levels of mRNA expressions and protein activities. The relationship between plasminogen activator/plasmin and the activation of MMP-2/9 was also investigated. The results showed that fibrin treatment induced a dramatic expression of activated MMP-2 and MMP-9 in HMC in a dose and time dependent manner. Fibrin zymography showed that fibrin also induced the expression of tissue type plasminogen activator (tPA) as well as urokinase type plasminogen activator (uPA). Inhibiting the activity of plasmin by aprotinin could totally block the conversion of pro-MMP-2/9 to active enzyme. The results suggested that fibrin deposition might play an important role in regulating the MMP-2/9 expressions in HMC, contributing to the remodeling of extracellular matrix. The activation of proMMP-2/9 may depend on PA/plasmin activation.

关 键 词：纤维蛋白 系膜细胞 明胶酶A 明胶酶B 纤溶酶原激活剂 肾病 

分 类 号：R692[医药卫生—泌尿科学] Q556.3[医药卫生—外科学]