摘要
目的探讨p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)和环氧化酶-2(cvclooxygenase-2,COX-2)的关系,从而研究p38MAPK和COX-2在糖尿病肾病中的作用及硒在防治糖尿病肾病中的作用机制。方法分别以高葡萄糖、高胰岛素、过氧化氢和糖基化终末产物孵育大鼠肾小球系膜细胞系HBZY-1;先给予p38MAPK特异性抑制剂SB203580和亚硒酸钠分别预处理细胞系HBZY-1后,再给予上述4种因素孵育细胞系HBZY-1,观察细胞系HBZY-1 p38MAPK和COX-2的蛋白表达。结果高葡萄糖、高胰岛素、过氧化氢和糖基化终末产物均可独立激活p38MAPK,使其磷酸化表达量增加,COX-2蛋白表达也明显增加;SB203580预处理后,COX-2蛋白表达被显著抑制;亚硒酸钠预处理后,p38MAPK磷酸化被明显抑制,同时COX-2蛋白表达明显降低。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在糖尿病肾病的发生发展过程中起重要作用;亚硒酸钠可通过抑制p38MAPK而抑制COX-2表达,从而表明硒能有效地防治糖尿病肾病。
Objective To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK） and cyclooxygenase-2 （COX-2） and their role in genesis of diabetic nephropathy, and therefore to study the mechanism of sodium selenite in preventing diabetic nephropathy. Methods Initially, expressions of p38MAPK and COX-2 were detected in rat mesangial cell line HBZY-1 which were incubated respectively with 25 mmol/L glucose, 100 nmol/L insulin, 100 μmol/L H2O2 and 100 mg/L AGEs. The relationship between p38MAPK and COX-2 protein expression was investigated by using SB203580, a specific inhibitor of p38MAPK. The direct effects of sodium selenite were then determined on the regulation of p38MAPK and COX-2 protein expression. Results p38MAPK and COX-2 had significantly higher expression in rat mesangial cells line HBZY-1 incubated with 25 mmol/L glucose, 100 nmol/L insulin, 100 μmol/L H2O2 and 100 mg/L AGEs respectively. COX-2 activity was significantly reduced when p38MAPK was inhibited by SB203580. Furthermore, both p38MAPK and COX-2 protein expression were significantly decreased in rat mesangial cell line HBZY-1 with sodium selenite treatment. Conclusions p38MAPK and COX-2 are involved in the development of diabetic nephropathy and p38MAPK stimulation is essential for COX-2 expression, and sodium selenite may play a role in the prevention of diabetic nephropathy by down-regulating both p38MAPK and COX-2 expression.
出处
《中国地方病学杂志》
CAS
CSCD
北大核心
2006年第2期164-167,共4页
Chinese Jouranl of Endemiology
基金
国家自然科学基金资助项目(30370670)
