内质网应激在高糖所致血管平滑肌细胞钙化中的作用与机制  

Role and Mechanism of ER Stress in Vascular Smooth Muscular Cell Calcification Induced by High Glucose

作　　者：刘畅[1] 吴斌[1] 李兴岳 吴子君[1] 姜佳美[1] 游琼[1] 吴铿[1] 郭润民[1] 

机构地区：[1]广东医学院附属医院心血管内科,湛江524001

出　　处：《成都医学院学报》2015年第5期531-534,共4页Journal of Chengdu Medical College

基　　金：广东省自然科学基金博士启动项目(No:2015A030310359);湛江市财政资金科技专项竞争性分配项目(No:2014A01033);广东省重大科技专项(No:2012A080202020);湛江市第二批科技计划项目(No:2012C0303)

摘　　要：目的探讨内质网(endoplasmic reticulum,ER)应激在高糖引起的血管平滑肌细胞(vascular smooth muscle cells,VSMCs)钙化中的作用与机制。方法 35mmol/L D-葡萄糖(高糖)处理VSMCs,模拟糖尿病状态,观察高糖能否引起VSMCs的ER应激和VSMCs表型转化(收缩型转变为成骨样细胞),观察ER应激的抑制剂对VSMCs钙化的效应,采用比色法、o-cresolphthalein法和western blot观察碱性磷酸酶活性、钙沉积和骨分化转录因子(Runx2)等指标。结果应用35mmol/L D-葡萄糖分别处理VSMCs 3d或7d,可引起VSMCs的ER应激蛋白表达上调、碱性磷酸酶活性增加、钙沉积和骨分化标志蛋白增多;苯基丁酸(4-phenylbutyric acid,4-PBA)预处理在抑制VSMCs的ER应激的同时,能阻断高糖所致VSMCs钙化(表现为碱性磷酸酶活性、钙沉积和骨分化标志蛋白下降)。结论高糖能激活VSMCs的ER应激,继而引起VSMCs凋亡和钙化,提示ER应激在高糖引起的VSMCs钙化中起着重要作用。Objective To investigate the role and mechanism of endoplasmic reticulum（ER）stress response in calcification of vascular smooth muscle cells（VSMCs）induced by high glucose.Methods VSMCs mimicked Diabetes was treated with 35 mmol/L D-glucose to observe whether high glucose could induce ER stress response and calcification of VSMCs.Effects of ER stress inhibitor on calcification of VSMCs was observed.ALP activity,calcium content and osteogenic markers expression were tested using colorimetric assay,o-cresolphthalein method and Western blot analysis.Results Treating VSMCs with 35 mmol/L D-glucose for 3dor 7dcould induce ER stress and osteoblastic differentiation of VSMCs（ALP activity,calcium content and osteogenic markers expression increase）.4-phenylbutyric acid（4-PBA）pre-treatment could inhibit ER stress of VSMCs and high glucose-elicited vascular SMCs calcification.Conclusion High glucose can activate ER stress,apoptosis and osteoblastic differentiation of VSMCs which demonstrates the important role of ER stress in VSMCs calcification induced by high glucose.

关 键 词：糖尿病 高糖 内质网应激 血管平滑肌细胞 血管钙化 

分 类 号：R543[医药卫生—心血管疾病]