高糖刺激内质网应激诱导单核细胞活化  

Effect of endoplasmic reticulum stress on the activation of high glucose- induced monocytes

作　　者：黄丽[1] 冯兵[1] 庞琦[1] 陈吉刚[1] 郭艳红[1] 杜翔[1] 袁发焕[1] 

机构地区：[1]第三军医大学新桥医院肾内科全军肾脏病中心重庆市肾脏病研究所,重庆400037

出　　处：《中华肾脏病杂志》2013年第3期189-194,共6页Chinese Journal of Nephrology

基　　金：基金项目：国家自然科学基金（31100927）

摘　　要：目的探讨内质网应激在高糖诱导单核细胞活化中的作用。方法采用高糖刺激培养的单核细胞株（THP-1）。RT—PCR和Westen印迹法检测葡萄糖调节蛋白78（GRP78）、磷酸化c—Jun氨基末端蛋白激酶（p-JNK）等内质网应激反应指标变化以及分子伴侣甜菜碱干预后的改善效果。MTT法检测细胞增殖，Transwell小室法检测单核细胞的趋化能力。免疫荧光法检测单核细胞亚型。结果与正常对照组相比，GRP78mRNA和蛋白表达升高（P〈0．05）；p-JNK蛋白表达水平增加（P〈0．05）；单核细胞增殖活性和趋化能力增强，向M1亚型分化增多（P〈0．05）。分子伴侣甜菜碱可抑制高糖引起的单核细胞内质网应激反应、增殖活性和趋化能力，促使单核细胞向M2亚型分化。结论高糖通过刺激内质网应激而诱导单核细胞活化，甜菜碱可逆转高糖对单核细胞的激活作用。Objective To observe the effects of endoplasmic reticulum stress （ERS） on the activation of monocytes induced by high glucose and explore the underlying mechanism. Methods The monocyte cell line THP- 1 was stimulated with high glucose, and then treated with molecular chaperone betaine. The levels of glucose regulation protein 78 （GRP78） and p- 3NK, which were associated with ERS were detected by real-time PCR and Western blotting. The proliferation of the cell line was detected by MTT method. Transwell and immunofluorescence were applied to observe the chemotaxis and phenotype of cells respectively. Results The levels of GRP78 and p-JNK of THP- 1 cells stimulated by high glucose were significantly increased compared with the normal control group （all P 〈 0.05）. The proliferation and chemotactic were also enhanced （all P 〈 0.05）. The number of cells in M1 phenotype was increased remarkably （P 〈 0.05）. All the indexes above could be rescued by betaine. Conclusion The activation of THP- 1 cells can be induced by high glucose through ERS, while molecular chaperone betaine can reverse the activation.

关 键 词：内质网应激 单核细胞 高糖 甜菜碱 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]