1,25（OH）2D3通过MAPK/P38通路缓解高糖所致的小鼠腹膜上皮细胞-间充质转化

1,25 （OH）2D3 treatment attenuate high glucose-induced peritoneal EMT in mouse

目的 探讨1,25（OH）2D3对高糖所致小鼠腹膜EMT的影响及其作用机制.方法 4.25％高糖腹膜透析液腹腔注射建立小鼠腹膜上皮细胞-间充质细胞转分化（epithelial to mesenchymal transition,EMT）模型.35只昆明小鼠（28～30 g）随机分为以下七组：①空白对照组;②盐水对照组;③维生素D低剂量组（1 μg/kg）;④维生素D高剂量组（5μg/kg）;⑤腹透组;⑥腹透＋维生素D低剂量组;⑦腹透＋维生素D高剂量组.实验开始后第28天处死小鼠.Western blot及Real time PCR检测腹膜组织E-cadherin、FN、P38、p-P38等蛋白及基因的表达.结果 ①高糖透析液能显著上调FN表达水平,下调E-cadherin表达,提示腹膜发生了EMT改变.应用1,25（OH）2D3能够部分逆转腹膜EMT的发生;②高糖透析液能显著上调磷酸化P38蛋白表达水平,应用1,25（OH）2D3后能够部分下调腹膜间皮细胞磷酸化P38蛋白表达.结论 高糖能够刺激小鼠腹膜发生EMT,1,25（OH）2D3能够抑制高糖诱导的腹膜间皮细胞EMT,MAPK/P38信号通路参与了上述过程.

Objective To investigate the role of 1,25 （OH）2 D3 on high glucose（HG） induced EMT in peritoneal mesothelium.Methods Peritoneal dialysate（4.25 ％） was infused intraperitoneally to create the model of peritoneal mesothelium EMT.Thirty-five Kunming male mice（28-30 g） were randomly assigned into seven groups：control group,saline group,low dose vitamin D group,high dose vitamin D group,peritoneal dialysis （PD） group,low dose vitamin D ＋ PD group,high dose vitamin D ＋ PD group.We performed Western blot and Real-time PCR to detect the expression of E-cadherin,FN,P38 and p-P38.Results ①We found that high glucose PDF upregulated the expression of FN,down-regulated the expression of E-cadherin,which means HG promoted EMT.However,1,25 （OH）2D3 treatment attenuated the HG-induced EMT.②We found that high glucose-PDF upregulated the expression of p-P38.However,1,25 （OH）2D3 treatment down-regulated the expression of p-P38 induced by HG.Conclusions HG indeuced EMT,1,25 （OH） 2 D3 attenuates the high glucose-induced EMT in peritoneal mesothelium through MAPK/P38 pathways.