内质网应激在主动脉夹层中的发病作用及意义
Pathogenesis and significance of endoplasmic reticulum stress in aortic dissection
陈诚 1徐亚欢 2周倩1
作者信息
- 1. 黄石市中心医院(湖北理工学院附属医院)老年病科,湖北 黄石 435000
- 2. 黄石市中心医院(湖北理工学院附属医院)胸心血管外科 湖北 黄石 435000
- 折叠
摘要
目的:探讨主动脉夹层(AD)发病中内质网应激(ERS)表达水平变化及ERS在AD发病中的作用.方法:选取黄石市中心医院2017年1月至2020年1月确诊为急性Stanford A型AD并行胸主动脉置换患者为AD组,取自我院行心脏移植的供者正常主动脉组织作为对照样本(对照组),通过苏木素伊红(HE)染色、心肌弹性纤维EVG染色、细胞凋亡TUNEL染色、蛋白免疫印迹及荧光定量PCR检测主动脉中膜形态学、凋亡水平及ERS相关蛋白表达水平变化.使用β-氨基丙腈(BAPN)构建动物AD模型,同时对实验小鼠腹腔注射ERS抑制剂4-苯基丁酸(4-PBA)构建ERS干预组,造模成功后留取病变部位主动脉进行后续检测.结果:与对照组相比,AD组有明显主动脉假腔形成,主动脉中膜弹性纤维断裂明显,符合主动脉中膜退行性变,同时AD组ERS表达水平上调,使用 4-PBA后ERS水平下调,AD主动脉中膜凋亡率下降,夹层发病率下降.结论:AD发病过程中ERS水平上调,凋亡水平增加,抑制ERS水平可降低主动脉中膜的凋亡率,延缓AD的发生发展,ERS或可以作为AD干预的靶点.
Abstract
Objective:To investigate the changes in the expression level and the role of endoplasmic reticu-lum stress(ERS)in the pathogenesis of aortic dissection(AD).Methods:Patients who were diag-nosed with acute AD in Stanford type A and with a parallel thoracic aortic replacement from January 2017 to January 2020 in Huangshi Central Hospital were included in the AD group,and normal aortic tissue samples were set as controls from the healthy donors(control group)for heart transplantation in our hospital.The morphology of the aortic media,the level of apoptosis,and the expression of ERS-related proteins were detected by HE staining,EVG staining,TUNEL staining,Western blot,and fluorescence quantitative PCR.Beta-aminopropionitrile(BAPN)was used to construct the animal AD model,and the experimental mice were injected intraperitoneally with 4-phenylbutyric acid(4-PBA),an inhibitor of ERS,to construct the ERS intervention group.Results:Compared with the control group,the AD group had obvious aortic false cavity formation,and obvious rupture of elastic fibers in the aortic media,which was consistent with the degeneration of the aortic media.Meanwhile,the ex-pression level of ERS in the AD group was up-regulated,but the ERS level was down-regulated,and rates of aortic media apoptosis and incidence of AD were decreased after the use of 4-PBA.Conclu-sion:During the pathogenesis of AD,the apoptosis of aortic media and the level of ERS were up-regu-lated.Inhibiting the level of ERS can reduce the apoptosis rate of the aortic media and alleviate the oc-currence and development of AD.ERS may be a target for AD intervention.
关键词
主动脉夹层/内质网/应激/4-苯基丁酸Key words
Aortic Dissection/Endoplasmic Reticulum/Stress/4-Phenylbutyric Acid引用本文复制引用
基金项目
湖北省卫生健康委员会基金项目(WJ2019H491)
出版年
2024
NETL
NSTL
万方数据