高糖通过环加氧酶2依赖性途径诱导GRP78表达改变  

High glucose changes the expression of GRP78 in COX-2 dependent manner in HUVECs

作　　者：郑鸣之[1,2] 范莹[3] 孟香红[3] 朱立[3] 沈岳良[3] 陈莹莹[3] 

机构地区：[1]浙江大学基础医学国家理科人才培养基地,浙江杭州310058 [2]浙江医学高等专科学校药理教研室,浙江杭州310053 [3]浙江大学医学院生理教研室,浙江杭州310058

出　　处：《中国病理生理杂志》2009年第8期1576-1580,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30400094)

摘　　要：目的:观察高糖慢性处理对血管内皮细胞内质网应激标志蛋白葡萄糖调节蛋白78(GRP78)表达的影响及其作用机制。方法:培养的HUVECs细胞用含正常糖(5.5mmol/L)或高糖(30mmol/L)的培养基处理不同时间后,用MTT法测定细胞存活率,流式细胞仪测定细胞凋亡,Western blotting法测定蛋白表达情况。结果:与相应对照组相比,HUVECs细胞经高糖孵育24-48h后,GRP78蛋白表达量先增加后减少;而环加氧酶-2(COX-2)蛋白表达量逐渐增加。COX-2选择性抑制剂尼美舒利与高糖共孵育后,可明显抑制高糖引起的GRP78蛋白表达改变;同时尼美舒利可抑制高糖孵育48h后诱导的细胞凋亡。结论:高糖慢性处理可诱导HUVECs细胞GRP78表达先增加后减少,此过程依赖于COX-2蛋白的上调。AIM ： To investigate the effect of high glucose on the expression of an endoplasmic reticulum stress marker glucose - regulated protein 78 （ GRP78 ）, and explore its underlying mechanism. METHODS： （ 1 ） Human umbilical vein endothelial cells （HUVECs） were exposed to normal glucose （5.5mmol/L） and high glucose （30 mmol/L） for 24 h, 36 h or 48 h. Cell viability was determined by MTr method. Cell apoptosis was detected by flow cytometry analysis. The expression of proteins was evaluated by Western blotting analysis. RESULTS： After treated with high glucose for 24 -48 h, the expression of GRP78 increased early but decreased at 48 h of incubation, while cyclooxygenase -2 （COX - 2） expression increased in a time - dependent manner. COX - 2 selective inhibitor nimesulide inhibited high glucose in- duced changes of GRP78 expression and also inhibited high glucose induced cell apoptosis. CONCLUSION： Prolonged high glucose exposure changes the expression of GRP78 in a COX - 2 dependent manner in HUVECs.

关 键 词：高糖 葡萄糖调节蛋白78 环加氧酶-2 

分 类 号：R54[医药卫生—心血管疾病]