摘要
目的:探讨丝裂素活化蛋白激酶p38( p38MAPK )和血管内皮生长因子(VEGF)的关系,从而研究p38MAPK和VEGF在糖尿病肾病中的作用及硒在抗糖尿病肾病中的作用机制。方法:分别以高葡萄糖、糖基化终产物,高胰岛素和过氧化氢孵育大鼠肾小球系膜细胞(RMCs) ;以p38MAPK特异抑制剂SB2 0 35 80和亚硒酸钠分别预处理RMCs,再给予上述四种刺激因素孵育RMCs,观察RMCsp38MAPK和VEGF蛋白表达。结果:高葡萄糖、糖基化终产物、高胰岛素和过氧化氢均可独立激活p38MAPK ,使其磷酸化表达量增加,VEGF表达也明显增加:SB2 0 35 80预处理后,VEGF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VEGF表达显著降低。结论:p38MAPK调控VEGF的表达,表明p38MAPK和VEGF参与了糖尿病肾病的发生发展;亚硒酸钠可通过抑制p38信号通路而抑制VEGF的表达,从而有效地防治糖尿病肾病。
Objective:To investigate the relationship between p38 mitogen-activated protein kinase(p38MAPK) and vascular endothelial growth factor (VEGF),and to study the role of p38 mitogen-activated protein kinase and vascular endothelial growth factor for diabetic nephropathy,and therefore to study the mechanism of sodium selenite in anti-diabetic nephropathy.Methods:We initially investigated protein expression of p38MAPK and VEGF in rat mesangial cells(RMCs)which were incubated respectively with 25 mmol/L glucose,100mg/L BSA-AGEs,100nmol/L insulin and 100 μmol/L H 2O 2.We also studied the relationship between p38MAPK and VEGF protein expression by using SB203580,a specific inhibitor of p38MAPK.We then evaluated the direct effects of sodium selenite on the regulation of p38MAPK and VEGF protein expression.Results:p38MAPK and VEGF had significantly higher expression in RMCs incubated with 25mmol/L glucose,100mg/L BSA-AGEs,100nmol/L insulin and 100μmol/L H 2O 2 respectively.VEGF activity was significantly reduced when p38MAPK was inhibited by SB203580.Furthermore,both p38MAPK and VEGF protein expression were significantly decreased in RMCs with sodium selenite treatment.Conclusion:p38MAPK and VEGF are involved in development of diabetic nephropathy and p38MAPK stimulation is essential for VEGF expression,and also suggests that sodium selenite may play a role in the prevention of diabetic nephropathy by down-regulation of both p38MAPK and VEGF expression.
出处
《重庆医科大学学报》
CAS
CSCD
2005年第2期191-195,199,共6页
Journal of Chongqing Medical University
基金
国家自然科学基金 (3 0 3 70 670 )
关键词
亚硒酸钠
P38MAPK
VEGF
糖尿病肾病
大鼠肾小球系膜细胞
Sodium selenite
P38 mitogen-activated protein kinase
Vascular endothelial growth factor
Diabetic nephropathy
Rat mesangial cells