中文摘要：

目的：探讨p38丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase,p38MAPK）、核因子-κB（nuclearfactor-κB,NF-κB）和环氧化酶-2（cyclooxygenase-2,COX-2）之间的关系,从而研究p38MAPK和NF-κB、COX-2在糖尿病肾病中的作用机制。方法：分别以一定浓度的高葡萄糖（25mmol/L）、高胰岛素（100mmol/L）、过氧化氢（100μmol/L）和糖基化终产物（100mg/L）孵育大鼠肾小球系膜细胞系HBZY-1一定时间;先分别以一定浓度的p38MAPK特异抑制剂SB203580（10μmol/L）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、NF-κB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,NF-κB、COX-2表达也明显增加,与对照组比较有显著性差异（P〈0.01）;SB203580预处理后,NF-κB、COX-2表达显著降低,与相应刺激组比较差异有统计学意义（P〈0.01）。结论：p38MAPK可通过激活NF-κB、COX-2而诱导DM时肾脏的损害,p38MAPK和NF-κB、COX-2在糖尿病肾病的发生发展过程中可能起重要作用。

英文摘要：

Objective：To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK）, nuclear factor-κB （NF-κB） and cyclooxygenase-2 （COX-2）, so as to study the roles of p38MAPK, NF-κB and COX-2 in diabetic nephropathy. Methods： Rat mesangial cell line HBZY-1 was incubated with certain concentrations of glucose（25 mmol/L）, insulin （100 mmol/L）, H202 （100 mmol/L） and glycation endproducts （AGEs）（ 100 mg/L） with or without pretreatment with SB203580, a specific inhibitor of p38MAPK, then the expression of p38MAPK, NF-κB and COX-2 in the HBZY-1 cells was examined. Results： High glucose, high insulin, H2O2 and AGEs independently activated p38MAPK, increased p38MAPK phosphorylation, and significantly up-regulated the expression of NF-κB and COX-2 compared with the control group （P〈0.01）. Pretreatment with SB203580 significantly decreased expression of NF-κB and COX-2 compared with the corresponding stimulating group （P〈0.01）. Conclusion： p38MAPK may induce renal damage during diabetic nephropathy by activating NF-κB and COX-2, indicating that p38MAPK, NF-κB and COX-2 may play important roles in the development of diabetic nephropathy.