高糖环境通过激活P13K／Akt通路诱导巨噬细胞向M2分化  

High glucose induced macrophages polarized into M2 via activation of PI3K/Akt signaling pathway

作　　者：阮一平[1] 汪洁[2] 吴家斌[1] 洪富源[1] 高美珠[1] 

机构地区：[1]福建省立医院肾内科,福建医科大学省立临床学院,福州350001 [2]福建医科大学附属协和医院皮肤科

出　　处：《中华内分泌代谢杂志》2017年第11期976-981,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：福建省卫生和计划生育委员会青年科研课题（2014-1-1）

摘　　要：目的探讨高糖环境诱导巨噬细胞向M2分化的机制。方法体外培养小鼠永生化巨噬细胞系Raw264．7至80％融合时，加入含4．25％葡萄糖浓度的无血清培养基，以甘露醇制备相同渗透压的培养基做为对照，培养4、8、12h后收集细胞蛋白。应用Western印迹及间接免疫荧光技术检测M2表面标记CD206、Arg-1及P13K／Akt通路激活状况，应用PI3K特异性抑制剂LY294002抑制PI3K／Akt通路观察下游目标蛋白Arg-1的表达。结果体外高糖环境下Arg-1自8h起分泌较多，CD206在12h大量表达。高糖培养基培养Raw264．7至8h，PI3K／Akt通路显著激活。PI3K特异性抑制剂可显著抑制P13K／Akt通路的激活，随之Arg-1的表达明显下降。结论体外高糖环境可通过激活P13K／Akt通路诱导巨噬细胞向M2分化，且其作用与单纯高渗透压无关。Objective To study the mechanism of differentiation of high glucose induced M2 macrophages used by high glucose medium stimulation. Methods Raw264.7 （ murine macrophage cell line ） was cultured and stimulated by 4.25% glucose medium, and mannitol medium was used as osmotic pressure control. Cells were harvested at Oh, 4h, 8h and 12h to examine the expression of CD206 and Arg-1 and the activation of PI3K/Akt signaling pathway. After blocking the PI3K/Akt signaling pathway by LY294002 （ the specific inhibitor of PI3K） , the expression of Arg-1 was examined by western blot. Results The expression of Arg-1 was increased from 8h while CD206 reached the peak at 12h induced by high glucose which indicated the activation of M2 in a time-dependent manner. Akt was phosphorylated at 8h stimulated by high glucose medium. The specific inhibitor of PI3K reduced the expression of Arg-1 by blocking the phosphorylation of Akt. Conclusion High glucose, rather than high osmotic oressure, induced macrophages oolarized into M2 via activation of PI3K/Akt signaling pathway.

关 键 词：高糖 P13K/AKT通路 巨噬细胞 

分 类 号：R692.5[医药卫生—泌尿科学]