p38MAPK对大鼠肾小球系膜细胞表达COX-2的影响

A role of p38 mitogen-activated protein kinase (p38MAPK) in regulating the expression of cyclooxygenase-2(COX-2) in rat mesangial cells

目的探讨p38丝裂原活化蛋白激酶(p38MAPK)和环氧化酶2(COX-2)的关系,从而研究p38MAPK和COX-2在糖尿病肾病(DN)中的作用机制。方法分别以高葡萄糖、高胰岛素、过氧化氢和糖基化终产物孵育大鼠肾小球系膜细胞系HBZY-1;先以p38MAPK特异抑制剂SB203580预处理细胞系HBZY-1,再给予上述4种因素孵育细胞系HBZY-1,观察细胞系HBZY-1p38MAPK和COX-2的表达。结果高葡萄糖、高胰岛素、过氧化氢和糖基化终产物均可独立激活p38MAPK,使其磷酸化表达量增加,COX-2表达也明显增加;SB203580预处理后,COX-2表达被显著抑制。结论p38MAPK调控COX-2的表达,表明p38MAPK是COX-2的上游激酶之一,p38MAPK和COX-2可能在DN的发生发展过程中起重要作用。

Objective To investigate the relationship between p38MAPK and COX-2,and to study the role of p38MAPK and COX-2 in pathogenesis of diabetic nephropathy. Methods We initially investigated the protein expression of p38MAPK and the mRNA and protein expressions of COX-2 of rat mesangial cells （ cell line HBZy-1） which were incubated with 25 mmol/L glucose,l（D nmol/L insulin,l（D I.unol/L H202 and 100 mg/L BSA-AGEs respectively. We also studied the relationship between p38MAPK and COX-2 expressions by using a specific inhibitor （SB203580） of p38MAPK. Results Both p38MAPK and COX-2 had significantly higher expression in rat mesangial cells when incubated with 25 mmol/L glucose, 100 nmol/L insulin, 100 μmol/L H2O2 and 100 mg/L AGEs,respectively（P 〈0.01 ） ,and COX-2 activity was significantly reduced when p38MAPK was inhibited by SB203580（P 〈 0. 01 ）. Conclusion Both p38MAPK and COX-2 are involved in development of diabetic nephropathy and p38MAPK stimulation is essential for COX-2 expression.