中文摘要：

目的：观察亚硒酸钠对大鼠肾小球系膜细胞系HBZY-1表达p38丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase,p38MAPK）和过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptorγ,PPARγ）的影响,从而研究p38MAPK和PPARγ在糖尿病肾病形成中的作用及硒在防治糖尿病肾病中的作用机制.方法：在以下3种条件下培养细胞系：（1）分别以一定浓度高葡萄糖、高胰岛素、过氧化氢和AGEs刺激细胞系HBZY-1一定时间;（2）先给予p38MAPK特异性抑制剂SB203580或亚硒酸钠预处理细胞后,再分别以高葡萄糖、高胰岛素、过氧化氢和糖基化终产物4种因素孵育细胞系HBZY-1;（3）以不加任何刺激培养细胞系作为对照.RT-PCR法观察各种情况下细胞系HBZY-1 PPARγ mRNA的表达,Western印迹法观察磷酸化p38MAPK的表达.结果：4种刺激因素均可作为独立因素激活p38MAPK,使其磷酸化表达量增加,PPARγ表达量显著减少;SB203580能显著增加细胞系HBZY-1 PPARγ表达;亚硒酸钠能明显抑制细胞系HBZY-1p38MAPK磷酸化表达,而显著增加细胞系HBZY-1 PPARγ表达（P＜0.01）.结论：在大鼠肾小球系膜细胞,p38MAPK对PPARγ具有拮抗作用,亚硒酸钠明显增加细胞系HBZY-1 PPARγ表达,并具有类似PPARγ激动剂的作用.

英文摘要：

Objective：To observe the influences of sodium selenite on expression of p38 mitogen-activated protein kinase （p38MAPK） and peroxisome proliferator-activated receptor γ （PPARγ） in rat mesangial cells line HBZY-1, so as to study the role of p38MAPK and PPARγ in diabetic nephropathy and the mechanism by which sodium selenite prevents diabetic nephropathy. Methods： Rat mesangial cell line HBZY-1 was incubated with high glucose, high insulin, H2O2 and advanced glycosylation end products （AGEs） separately before and after HBZY-1 cells were pre-treated with SB203580 （p38MAPK special inhibitor）or sodium selenite. Cells receiving no stimulation were taken as control. The expression of p38MAPK protein and PPARγ mRNA was detected respectively by immunohistochemistry assay and RT-PCR in all groups and the results were compared. Results： High glucose, high insulin, H2O2 and AGEs all activated p38MAPK, increased phospho-p38MAPK expression and decreased the expression of PPARγ mRNA in rat mesangial cells line HBZY-1. The expressions of phospho-p38MAPK protein was markedly inhibited by sodium selenite, while the expression of PPARγ mRNA was significantly increased by SB203580 or sodium selenite in rat mesangial cells lines HBZY-1 （P〈0.01）. Conclusion： p38MAPK may antagonize the expression of PPARγ in rat mesangial cells lines HBZY-1. Sodium selenite, with a similar effect to the agonist of PPARγ,can obviously increase the expression of PPARγ.