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SATB1基因沉默介导NF-κB通路对冠心病小鼠主动脉内皮细胞炎症损伤的保护作用
作者:蒋长荣  马小峰 
单位:南华大学附属南华医院 心血管内科, 湖南 衡阳 421002
关键词:特异AT-序列结合蛋白1基因 NF-κB信号通路 冠状动脉粥样硬化性心脏病 主动脉内皮细胞 炎症 小鼠 
分类号:R541.4;R-33
出版年·卷·期(页码):2020·39·第一期(35-40)
摘要:

目的:探讨特异AT-序列结合蛋白1(SATB1)基因沉默介导NF-κB通路对冠状动脉粥样硬化性心脏病(CHD)小鼠主动脉内皮细胞炎症损伤的保护作用。方法:构建CHD小鼠模型,提取CHD小鼠和正常小鼠主动脉分别作为正常组和模型组。HE染色观察小鼠主动脉病理学变化,免疫组织化学法检测SATB1蛋白表达阳性率。取THP1作为Normal组,诱导内皮损伤后的细胞分为空白组、阴性对照组、SATB1-siRNA组、TNF-α组、TNF-α+SATB1-siRNA组。ELISA法测定各组细胞中TNF-α、IL-6、IL-10水平。qRT-PCR和蛋白质印迹法分别检测各组细胞中SATB1、NF-kB以及细胞间黏附因子-1(ICAM-1)和血管细胞黏附因子-1(VCAM-1)的mRNA和蛋白表达水平。结果:与正常组小鼠相比,模型组主动脉组织SATB1蛋白阳性表达显著升高(均P<0.05)。细胞实验中与Normal组相比,其余各组TNF-α、IL-6表达升高,IL-10表达降低,SATB1、ICAM-1、VCAM-1以及NF-κB水平上升(均P<0.05);空白组、阴性对照组以及TNF-α+SATB1-siRNA组各指标差异无统计学意义(P>0.05);与空白组比较,SATB1-siRNA组TNF-α、IL-6表达降低,IL-10表达增高,SATB1、ICAM-1、VCAM-1以及NF-κB水平下降(均P<0.05);TNF-α组TNF-α、IL-6表达增高,IL-10表达降低,SATB1、ICAM-1、VCAM-1以及NF-κB水平上升(均P<0.05)。结论:SATB1基因沉默能够抑制NF-κB信号通路的激活,对CHD内皮细胞炎症损伤具有保护作用。

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