探讨阿司匹林联合替格瑞洛对腹主动脉瘤生长的抑制作用及机制。

选取36 d的载脂蛋白E基因缺陷小鼠48只，随机分为5组。其中8只为生理盐水对照组，其余40只均采用血管紧张素Ⅱ（angiotensinⅡ, AngⅡ; 1000 ng·kg^-1·min^-1）持续皮下注射诱导腹主动脉瘤模型，根据不同干预方式分为AngⅡ组、阿司匹林组、替格瑞洛组、阿司匹林联合替格瑞洛组（双药联合组），每组10只。记录实验前和实验末各组小鼠的基础情况（包括体重、收缩压、总胆固醇、甘油三酯、血小板计数等），获取腹主动脉组织并采用免疫组化及蛋白免疫印迹等方法检测白细胞介素-1β（interleukin-1β, IL-1β）、肿瘤坏死因子α（tumor necrosis factor α, TNF-α）、基质金属蛋白酶（matrix metalloproteinase, MMP）-2和MMP-9的表达。多组间计量资料的比较采用单因素方差分析，进一步两组间的比较采用LSD-t检验。

5组小鼠总胆固醇、甘油三酯、实验前收缩压、血小板计数的差异均无统计学意义（P>0.05），仅实验末收缩压的组间差异有统计学意义（F = 53.670，P<0.05）。除对照组小鼠未形成腹主动脉瘤外，其他4组小鼠腹主动脉瘤成模率为50.0%~80.0%、破裂发生率为30.0%~50.0%。5组小鼠腹主动脉瘤直径的差异有统计学意义（F=25.470，P<0.05），其中AngⅡ组、阿司匹林组、替格瑞洛组腹主动脉瘤直径均明显大于双药联合组（P<0.05或0.01）。5组小鼠IL-1β、TNF-α及MMP-2、MMP-9蛋白表达水平的差异均有统计学意义（F=45.500、21.940、49.650、199.100，P<0.05或0.01），其中双药联合组各指标表达水平均明显低于AngⅡ组、阿司匹林组、替格瑞洛组（P<0.05），阿司匹林组、替格瑞洛组各指标表达水平均与AngⅡ组无明显差异（P>0.05）。

阿司匹林联合替格瑞洛可抑制小鼠腹主动脉瘤的形成及生长，这一作用可能与抑制腹主动脉内炎症反应有关。

To investigate the inhibitory effect and mechanism of aspirin combined with tigrelol on the growth of abdominal aortic aneurysm.

48 apolipoprotein E gene deficient mice for 36 days were randomly divided into 5 groups. Among them, 8 rats were in the normal saline control group, and the other 40 rats were induced by continuous subcutaneous injection of angiotensin Ⅱ(AngⅡ; 1000 ng·kg^-1·min^-1). According to different intervention methods, the 40 animals were divided into AngⅡ group, aspirin group, tegrerol group and aspirin combined with tegrerol group (dual drug combination group), with 10 rats in each group. The basic information of mice in each group were recorded before and at the end of the experiment, including body weight, systolic blood pressure, total cholesterol, triglyceride, platelet count, etc. The tissue of abdominal aorta was obtained, and interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), matrix metalloproteinase (MMP)-2 and MMP-9 were detected by immunohistochemistry and western blot. Univariate analysis of variance was used for comparison of measurement data between multiple groups, and LSD-t test was used for further comparison between the two groups.

There was no significant difference in total cholesterol, triglyceride, systolic blood pressure and platelet count between the five groups (P > 0.05), but there was significant difference in systolic blood pressure at the end of the experiment (F=53.670, P < 0.05). Except that the control group did not form abdominal aortic aneurysm, the modeling rate of abdominal aortic aneurysm in the other four groups was 50.0%~80.0%, and the rupture rate was 30.0%~50.0%. There was significant difference in the diameter of abdominal aortic aneurysm among the five groups (F=25.470, P < 0.05), and the diameter of abdominal aortic aneurysm in AngⅡ group, aspirin group and tigrelol group was significantly larger than that in the combination group (P < 0.05 or P < 0.01). The expression levels of IL-1β, TNF-α, MMP-2, MMP-9 in 5 groups were significantly different (F=45.500, 21.940, 49.650, 199.100, P < 0.05 or P < 0.01). The expression levels of all indexes in the two-drug combination group were significantly lower than those in the AngⅡ group, aspirin group and ticagrelor group (P < 0.05), and there was no significant difference in the expression levels of all indexes in aspirin group and ticagrelor group compared with the AngⅡ group (P > 0.05).

Aspirin combined with ticagrelor can inhibit the formation and growth of abdominal aortic aneurysm in mice, which may be related to the inhibition of inflammatory response in abdominal aorta.