P38信号通路在人脐静脉内皮细胞表达环氧化酶-2中的作用

Role of P38 mitogen-activated protein kinase in expressing of cyclooxygenase-2 in human umbilical vein endothelial cells

目的:探讨P38信号通路(P38MAPK)在人脐静脉内皮细胞(HUVEC)表达环氧化酶2(COX2)的作用,从而研究P38MAPK在糖尿病动脉粥样硬化中的作用。方法:分别以高葡萄糖、糖基化终产物(AGE)、高胰岛素和过氧化氢刺激HUVEC;检测P38MAPK和COX2在HUVEC的蛋白表达。以P38MAPK特异性抑制剂SB203580预处理HUVEC后,再用上述四种因素刺激HUVEC,检测COX2在HUVEC的蛋白表达。结果:高葡萄糖、AGE、高胰岛素和过氧化氢均可独立激活P38MAPK,使磷酸化P38MAPK表达量增加,COX2蛋白表达量也增加;SB203580预处理后,COX2表达被显著抑制。结论:P38MAPK调控COX2的表达,它是COX2的上游信号分子,可能是动脉粥样硬化发生的始动信号之一。

Objective: To investigate the role of P38 mitogen-activated protein kinase (P38MAPK) in expressing cyclooxygenase-2 (COX-2) in human umbilical vein endothelial cells (HUVEC), in order to study the role of P38MAPK on diabetic atherosclerosis. Methods: HUVEC are separately stimulated with high glucose, advanced glycosylation end products (AGE), high insulin and H_(2)O_(2), the expression of phospho-P38MAPK and COX-2 is detected; Simultaneously, HUVEC pre-treated with SB203580 (P38MAPK special inhibitor) are stimulated with above stimulating factors, the expression of COX-2 is detected. Results: High glucose, AGE, high insulin and H_(2)O_(2 ) can activate P38MAPK and increase the expression both of phospho-P38MAPK and COX-2 significantly; But the expression of COX-2 is inhibited by SB203580. Conclusion: P38MAPK regulates the expression of COX-2; P38MAPK is a upstream signal molecule of COX-2 and P38MAPK may be one of initial signals on atherosclerosis occurrence.