硝化应激参与同型半胱氨酸诱导的血管内皮细胞自噬降低  

Nitrative stress participates in Hcy-induced autopahgic deficiency in vascular endothelial cells

作　　者：周艺[1] 严文静 甄攀攀[2] 张赏月 王雯[1,3] ZHOU Yi;YAN Wenjing;ZHEN Panpan;ZHANG Shangyue;WANG Wen(Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学基础医学院生理学与病理生理学系,北京100069 [2]首都医科大学附属北京潞河医院病理科 [3]代谢紊乱相关心血管疾病北京市重点实验室

出　　处：《中南医学科学杂志》2018年第6期572-575,579,共5页Medical Science Journal of Central South China

基　　金：国家自然科学基金(81671382)

摘　　要：本研究旨在探讨硝化应激与同型半胱氨酸(Hcy)诱导血管内皮细胞自噬降低之间的关系。利用饮食法建立高同型半胱氨酸血症(HHcy)大鼠模型,利用免疫组织化学染色法分别检测大鼠胸主动脉自噬相关蛋白及硝化应激相关蛋白的表达。体外培养人脐静脉内皮细胞,用Hcy刺激内皮细胞,提取细胞蛋白,检测自噬相关蛋白及硝化应激相关蛋白的表达。利用Fe TMPyP预处理Hcy刺激的HUVECs细胞,检测上述相关蛋白表达的变化。结果显示HHcy大鼠模型建立成功,同时其胸主动脉LC3表达下降,p62表达增加,NT表达增加; Hcy处理的HUVECs自噬水平明显降低,而Fe TMPyP预处理能够降低NT表达,逆转Hcy导致的细胞自噬水平降低。本研究表明硝化应激参与了同型半胱氨酸诱导的血管内皮细胞自噬降低。The aim of the study is to explore the relationship between nitrative stress and autophagic deficiency induced by homocystein （Hcy） in vascular endothelial cells. In diet-induced hyperhomocysteinemia （HHcy） rat model, the expression of nitrative stress-related and autophagy-related proteins was detected with immunohistochemistry in thoracic aorta. HUVECs were challenged with Hcy, then the total proteins were extracted to evaluate the autophagy level with Western Blot. Moreover, HUVECs were pre-treated with FeTMPyP, and the expressions of autophagy-related proteins were examined. The diet-induced HHcy rat model was established successfully. As the results showed, the autophagy level was decreased in thoracic aorta of HHcy rats. Meanwhile, the autophagy level was decreased significantly evidenced by decreased LC3 Ⅱ/Ⅰ expression and increased p62 expression. Moreover, the expression of NT were increased in both HHcy rats and Hcy-treated HUVECs. More importantly, pretreatment with FeTMPyP alleviated Hcy-induced autophagic deficiency significantly. These results indicated that elevated nitrative stress was involved in Hcy-induced autopahgic deficiency in vascular endothelial cells.

关 键 词：同型半胱氨酸 自噬 硝化应激 

分 类 号：R33[医药卫生—人体生理学]