慢性内质网应激诱导的凋亡在动脉粥样硬化斑块形成中的作用  

Role of chronic endoplasmic reticulum stress induced apoptosis in atherosclerotic plaque formation

作　　者：景怡[1,2] 蔡丹凤 林超[1] 孙鑫[1] 卞慧敏[1,3] JING Yi CAI Dan-Feng LIN Chao SUN Xin BIAN Hui-Min(College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210046, China College of Chemical Engineering, Huaiyin Institute of Technology, Huai ＇ an, Jiangsu 223003, China Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing, Jiangsu 210046, China)

机构地区：[1]南京中医药大学药学院,江苏省南京市210046 [2]淮阴工学院化工学院,江苏省淮安市223003 [3]江苏省中药药效与安全性评价重点实验室,江苏省南京市210046

出　　处：《中国动脉硬化杂志》2017年第9期957-962,共6页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(81173190);江苏省中医药管理局项目(LZ11191);江苏省高校优势学科建设工程资助项目(ysxk-2010);南京中医药大学中药学一级学科开放课题资助(2011zyx4-004);国家科技重大专向:重大新药创制(2011ZX09102-002-07)

摘　　要：内质网应激(ERS)与促进动脉粥样硬化(As)的非动脉壁系统和动脉壁系统因素均密切相关。未折叠蛋白反应(UPR)作为ERS长期激活的标志,可导致细胞的病理状态及组织功能受损。已有大量研究表明As斑块内的细胞,尤其是易损斑块区域的内皮细胞和巨噬细胞均表现有UPR被慢性激活。病理性的慢性ERS通过诱导细胞(内皮细胞、巨噬细胞及平滑肌细胞)凋亡而促进坏死核形成,激活炎症信号通路,影响易损斑块的形成与稳定性,有重要的促As效应。造成慢性ERS的应激源:氧化应激、氧化型胆固醇、细胞内高水平胆固醇及饱和脂肪酸等在As病程中表现明显,且在肥胖、胰岛素抵抗及糖尿病等促进As临床病程的因素中更为突出。近年研究已经部分揭示了ERS促As易损斑块形成的机制及体内的相关性,为ERS药物靶向性治疗途径提供了思路,但仍需大量深入的研究才能转化为具有临床意义的防治方法。The endoplasmic reticulum stress （ERS） has emerged as a factor that is relevant to a number of systemic and arterial-wall factors that promote atherosclerosis （As）. Prolonged activation of ERS pathway known as the unfolded protein response （UPR） can lead to cell pathology and subsequent tissue dysfunction. There is now ample evidence that the UPR is chronically activated in atherosclerotic lesional cells, particularly advanced lesional macrophages and endothelial cells. The stressors in advanced lesions that can lead to prolonged activation of the UPR include oxidative stress, oxyste- rols, and high levels of intracellular cholesterol and saturated fatty acids. These arterial-wall stressors may be especially prominent in the settings of obesity, insulin resistance, and diabetes, all of which promote the clinical progression of As. While exciting work over the last decade has begun to shed light on the mechanisms and in vivo relevance of ERS-driven As, much more work is needed to fully understand this area and to enable an informed approach to therapeutic translation.

关 键 词：内质网应激 动脉粥样硬化 未折叠蛋白反应 内皮细胞 巨噬细胞 

分 类 号：R363[医药卫生—病理学]