SHP2对小鼠腹主动脉瘤的作用及相关分子机制  

Effect of SHP2 on abdominal aortic aneurysm in mice and related molecular mechanisms

作　　者：郭爱林 李宇 苏力德 刘健磊 刘宗泓 Guo Ailin;Li Yu;Su Lide;Liu Jianlei;Liu Zonghong(Xiang'an Hospital of Xiamen University,Xiamen 361101,China)

机构地区：[1]厦门大学附属翔安医院心脏大血管外科,厦门361101

出　　处：《解剖学杂志》2024年第5期393-397,共5页Chinese Journal of Anatomy

基　　金：厦门市科学技术局文件(3502Z20214ZD1126)。

摘　　要：目的:探究含Src同源2结构域蛋白酪氨酸磷酸酶2(SHP2)对小鼠腹主动脉瘤的作用及相关分子机制。方法:灌注血管紧张素Ⅱ和使用高脂饲料饲养构建小鼠腹主动脉瘤模型,将其分为对照组、模型组与抑制剂组(注射SHP2抑制剂PHPS1),Masson和EVG染色检查小鼠腹主动脉病理变化。免疫印迹检测相关蛋白烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2)、硫氧还蛋白相互作用蛋白(TXNIP)、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、白细胞介素(IL)-1β、IL-18、基质金属蛋白酶(MMP)2和MMP9的表达水平。免疫荧光染色检测腹主动脉壁中MMP9和巨噬细胞F4/80的表达情况。结果:与模型组相比,抑制剂组的腹主动脉直径的扩张和动脉壁弹力纤维损坏加剧,巨噬细胞数量增多;抑制剂组小鼠腹主动脉组织中的相关蛋白NOX2、TXNIP、NLRP3、IL-1β、IL-18、MMP2、MMP9的蛋白表达水平增加,SHP2的蛋白表达水平显著降低。结论:SHP2可通过抑制巨噬细胞中的NLRP3信号通路和MMP2、MMP9的表达以减弱小鼠腹主动脉瘤的发展。Objective:To investigate the role and molecular mechanism of Src homology 2 domain-containing phosphatase 2(SHP2)in mouse abdominal aortic aneurysm.Methods:The mouse abdominal aortic aneurysm model was established by angiotensinⅡperfusion and high-fat diet feeding.The mice were divided into control group,model group,and inhibitor group(injected with SHP2 inhibitor PHPS1).The changes in mouse abdominal aortic pathology were examined using Masson and EVG staining.The expression levels of related proteins SHP2,NOX2,TXNIP,NLRP3,IL-1β,IL-18,MMP2,MMP9 were detected by Western blotting.The expression of MMP9 and F4/80 in the abdominal aortic wall were examined using immunofluorescence staining.Results:Compared with the model group,the inhibitor group showed exacerbated dilation of the abdominal aortic diameter,damage to the arterial wall elastic fibers,and an increase in the number of macrophages.The protein expression levels of NOX2,TXNIP,NLRP3,IL-1β,IL-18,MMP2,MMP9 in the abdominal aortic tissue of the inhibitor group mice increased,while the protein expression level of SHP2 significantly decreased.Conclusion:SHP2 can attenuate the development of mouse abdominal aortic aneurysm by inhibiting the NLRP3 signaling pathway and the expr ession of MMP2 and MMP9 in macrophages.

关 键 词：腹主动脉瘤 巨噬细胞 含Src同源2结构域蛋白酪氨酸磷酸酶 SHP2抑制剂 小鼠 

分 类 号：R364[医药卫生—病理学] R543.16[医药卫生—基础医学]