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

发布时间：2018-10-04 21:14

【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。
[Abstract]:Endoplasmic reticulum stress (ERS) is closely related to the non-arterial wall system and arterial wall system factors that promote atherosclerotic (As). Unfolded protein response (UPR), as a marker of long-term activation of ERS, can damage the pathological state and tissue function of the cells. A large number of studies have shown that UPR is chronically activated in cells in As plaques, especially endothelial cells and macrophages in vulnerable plaque areas. Pathological chronic ERS promotes the formation of necrotic nuclei by inducing apoptosis of endothelial cells, macrophages and smooth muscle cells, activates inflammatory signaling pathway, affects the formation and stability of vulnerable plaques, and has an important promoting effect on As. The stressors of chronic ERS, such as oxidative stress, oxidative cholesterol, high intracellular cholesterol and saturated fatty acids, were significant in the course of As, and were also found to be obese. Insulin resistance and diabetes are more prominent among the factors that promote the clinical course of As. Recent studies have partially revealed the mechanism of ERS promoting the formation of vulnerable plaque of As and its correlation in vivo, which provides a way for the drug targeting treatment of ERS. However, a large number of in-depth studies are still needed to transform it into a clinically significant prevention and treatment method.
【作者单位】：南京中医药大学药学院;淮阴工学院化工学院;江苏省中药药效与安全性评价重点实验室;
【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)
【分类号】：R543.5

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