高糖对培养的肾小球系膜细胞产生t-PA及与其结合的影响

Effects of high glucose on tissue plasminogen activator produced by cultured glomerular mesangial cells and its binding ability to the cells

目的 观察高糖状态下系膜细胞与组织型纤溶酶原激活物 (Tissueplasminogen ,t PA)结合力及系膜细胞产生t PA活性改变与纤维连接蛋白 (Fibronectin ,FN)产生的影响。方法 采用体外人肾小球系膜细胞培养 ,放射性核素标记法测定系膜细胞与t PA结合力 ,纤维蛋白酶谱法检测t PA活性 ,酶联免疫分析检测FN。结果 高糖可抑制系膜细胞与t PA结合力 ,同时t PA活性增加 ,FN产生明显增多 ,并随着培养时间的延长 ,葡萄糖愈高 ,作用愈明显。结论 高糖致系膜细胞与t PA结合力下降 ,t PA活性增加 ,同时可能其抑制物明显增多 ,导致细胞外基质积聚 ,可能是糖尿病肾病肾小球硬化发生的重要原因之一。

Objective To observe the effects of high glucose on the production of tissue plasminogen activator (t PA) by human glomerular mesangial cells (MC), its binding ability to the cells, and the role of fibronectin (FN) in this event. Methods Human MC were isolated and cultured under a high glucose condition. Fibrin enzymography was used to measure the activity of t PA, and radioassay to detect the binding ability of t PA to MC. FN was detected with ELISA. Results High glucose supressed the binding ability of t PA to MC while significantly increased the production of t PA and FN by MC. With the longer the MC were cultured with high glucose, the higher the concentration of glucose was, the more significant the effect was. Conclusion High glucose inhibits the binding ability of t PA to MC and the t PA activity is increased. At the same time, its inhibitor may increase significantly. All these factors may cause the accumulation of extracellular matrix, and contribute to glomerular sclerosis in patients with diabetic nephropathy.