p38MAPK对大鼠肾小球系膜细胞表达PPAR-γ的影响

A role of p38 mitogen-activated protein kinase in regulating expression of Peroxisome proliferator-activated receptors-γ in rat mesangial cells

目的探讨p38丝裂原活化蛋白激酶(p38mitogen-activatedproteinkinase,p38MAPK)和过氧化物酶体增殖物激活受体-γ(peroxisomeproliferator-activatedreceptors-γ,PPAR-γ)的关系,从而研究p38MAPK和PPAR-γ在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产物孵育大鼠肾小球系膜细胞系HBZY-1;先分别以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PPAR-γ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,PPAR-γ表达明显减少;SB203580预处理后,PPAR-γ表达显著增加。结论在大鼠肾小球系膜细胞,p38MAPK对PPAR-γ具有拮抗作用,表明PPAR-γ的激活可能具有直接的肾脏保护作用。

Objective To investigate the relationship between p38MAPK and PPAR-γ, and to study the role of p38MAPK and PPAR-γ for diabetic nephropathy. Methods The expression of p38MAPK protein and PPAR-γ mRNA was investigated in rat mesangial cells line HBZY-1 that was 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 PPAR-γ expression was studied by using SB203580, a specific inhibitor of p38MAPK. Results p38MAPK had significantly higher expression, while the expression of PPAR-γ was significantly decreased 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. PPAR-T activity was significantly reduced when p38MAPK was inhibited by SB203580. Conclusion p38MAPK is involved in development of diabetic nephropathy and may antagonize the expression of PPAR-T. PPAR-T activity might protect the function of kidney.