血管生成素1在高同型半胱氨酸血症大鼠血浆中高表达及对内皮细胞的保护作用  

Study on the high expression of angiopoietin 1 in plasma of hyperhomocysteinemia rats and its protective effect on endothelial cells

作　　者：沈童童[1] 周利民[1] 董双双 王欣欣[1] 徐小红[1] 刘玉[1] 郑凡 马劭博 沈兵[2] Shen Tongtong;Zhou Limin;Dong Shuangshuang;Wang Xinxin;Xu Xiaohong;Liu Yu;Zheng Fan;Ma Shaobo;Shen Bing(Dept of Cardiology,The Affiliated Chuzhou Hospital of Anhui Medical University(The First People′s Hospital of Chuzhou),Chuzhou 239000;Dept of Physiology,School of Basic Medical Science,Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学附属滁州医院(滁州市第一人民医院)心内科,滁州239000 [2]安徽医科大学基础医学院生理教研室,合肥230032

出　　处：《安徽医科大学学报》2022年第5期679-683,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81570403);滁州市科技计划项目(编号:2019ZN008)。

摘　　要：目的阐明高同型半胱氨酸(Hcy)血症大鼠血浆蛋白表达谱改变及高表达的血管生成素1(Ang 1)对内皮细胞的保护作用。方法建立高Hcy血症动物模型,采用Label-free蛋白质谱分析血浆蛋白含量差异,细胞划痕和CCK-8实验检测Hcy及Ang 1对内皮细胞迁移和增殖的影响。结果蛋白质谱结果显示高Hcy血症大鼠血浆中有5个蛋白上调、17个蛋白下调,其中Ang 1上调。大鼠肠系膜上动脉内皮细胞实验结果显示,采用30、50μmol/L Hcy预处理内皮细胞24 h后,细胞的迁移和增殖都被抑制,而Ang 1(600 ng/ml)阻断了30μmol/L Hcy对内皮细胞迁移和增殖的抑制作用,但对50μmol/L Hcy引起的内皮细胞迁移和增殖抑制作用无阻断效应。结论高Hcy血症可影响血浆蛋白表达谱,血浆中升高的Ang 1可代偿一定浓度范围Hcy对血管内皮细胞的迁移和增殖的抑制作用。Objective To investigate the changes of plasma protein expression profile in hyperhomocysteinemia rats and the protective effect of highly expressed angiopoietin 1 in plasma on endothelial cells.Methods The hyperhomocysteinemia animal model was established.The difference in plasma protein content was analyzed by label-free protein spectroscopy.The effects of homocysteine and angiopoietin 1 on endothelial cell migration and proliferation were detected by wound healing and CCK-8 proliferation assay.Results The results of protein profiling showed that 5 proteins were significantly up-regulated and 17 proteins were significantly down-regulated in the plasma of hyperhomocysteinemia rats,among which angiopoietin 1 was significantly up-regulated.In endothelial cells in the superior mesenteric artery of rats,treatment with 30 or 50μmol/L homocysteine for 24 h significantly inhibited the migration and proliferation.Angiopoietin 1(600 ng/ml)significantly reduced the migration and proliferation of endothelial cells inhibited by 30μmol/L homocysteine,but had no significant effect on the migration and proliferation of endothelial cells inhibited by 50μmol/L homocysteine.Conclusion Hyperhomocysteinemia can significantly affect the protein expression profile in plasma.Angiopoietin 1 in plasma can compensate for the damage of vascular endothelial migration and proliferation function caused by homocysteine in a certain concentration range.

关 键 词：同型半胱氨酸 血管生成素1 血管内皮细胞 Label-free蛋白质谱 迁移 增殖 

分 类 号：R363.21[医药卫生—病理学]