内质网应激与血管内皮细胞功能障碍关系研究进展.docVIP

内质网应激与血管内皮细胞功能障碍关系研究进展 　　[摘要] 内质网是调控细胞蛋白质合成、钙稳态和细胞凋亡的重要细胞器，内皮细胞具有高度发达的内质网，越来越多的研究发现内质网应激参与内皮细胞功能障碍。多种病理状态如高同型半胱氨酸血症、高血流剪切应力、高脂血症、高血糖等都可引起内皮细胞发生内质网应激，适当的内质网应激通过激活未折叠蛋白反应恢复内质网稳态，而内皮细胞内质网功能的长期损伤将导致慢性内质网应激和未折叠蛋白反应，进而增加内皮细胞氧化应激和炎性反应，最终致死亡。由于内皮细胞在维持血管稳态中作用关键，其收缩舒张功能障碍，且内皮细胞分泌的血管活性物质失衡，是多种血管性疾病发病的重要环节，尤其在体循环高血压和肺高血压病理生理过程中起着关键作用。 　　[关键词] 内质网应激；未折叠蛋白反应；内皮细胞功能障碍；肺动脉高压 　　[中图分类号] R544.1 [文献标识码] A [文章编号] 1673-7210（2015）09（c）-0030-05 　　[Abstract] Endoplasmic reticulum is an important organellein regulating protein synthesis， calcium homeostasis and apoptosis. It is known that endothelial cells have highly developed endoplasmic reticulum. Recently， a growing number of studies have found endoplasmic reticulum stress involved in endothelial dysfunction. A various pathological conditions including homocysteinemia， high blood flow shear stress， hyperlipidemia， high glucose can lead to endothelial dysfunction in part through theactivation of ER stress. Proper endoplasmic reticulum stress helps maintain the balance of endoplasmic reticulum by activating unfolded protein response， whilechronic activation of ER stress and UPR pathways inendothelial cells causes a rise of oxidative stress andinflammatory responses， eventually lendingto cell death. Endothelialcells play a crucial role in maintaining vascular homeostasis. It is theloss of normal systolic and diastolic function and the imbalance of endothelial-cell- secreted vasoactive substances that result in a variety of vascular diseases， especially systemic hypertension and pulmonary arterial hypertension. 　　[Key words] Endoplasmic reticulum stress； Unfolded protein response； Endothelialdysfunction； Pulmonary arterial hypertension 　　内质网（endoplasmic reticulum，ER）在许多细胞生命过程中起重要生理调控作用。越来越多的证据表明，ER功能障碍诱发的信号网络既能使细胞自适应，也可促细胞凋亡。病理条件下，ER稳态遭破坏，缓慢激活未折叠蛋白反应（unfolded protein response，UPR），长期的ER应激（endoplasmic reticulum stress，ERS）参与许多疾病发生，包括神经退行性变，动脉粥样硬化，2型糖尿病，肝脏疾病和癌症[1-2]。正常内皮细胞在维护血管的通透性，调节组织与血液的物质交换，调节血管张力，调控炎性免疫反应，维持血流通畅等方面发挥重要作用。研究表明，内皮细胞功