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 angiotensin Ⅱ perfusion 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.