苯并[a]芘诱导小鼠腹主动脉瘤形成机制研究

Benzo[a]pyrene(BaP) promotes abdominal aortic aneurysm formation in mice and its mechanism

目的：探讨香烟烟雾重要成分苯并[a]芘（BaP）诱导小鼠腹主动脉瘤（AAA）形成的相关机制。方法48只7~9月龄C57BL/6N小鼠分为对照组、血管紧张素Ⅱ（AngⅡ）组、BaP组、AngⅡ/BaP复合物组。5周后取各组小鼠腹主动脉观察大体标本形态,切片行HE染色观察血管结构；免疫组化法检测各组靶血管基质金属蛋白酶-3（MMP-3）、核转录因子-κappaB（NF-κB）的表达, POD法TUNEL检测血管平滑肌细胞凋亡情况。结果大体标本显示AngⅡ/BaP复合物组腹主动脉瘤形成率为41.67%，明显高于AngⅡ组腹主动脉瘤形成率25.00%（P＜0.05），HE染色提示动脉瘤形成处弹性纤维紊乱血管壁显著变薄。免疫组化提示AngⅡ/BaP复合物组MMP-3及NF-κB的表达均较AngⅡ组及BaP组增加[（0.48±0.13）% vs （0.24±0.16）%，（0.34±0.10）%；（0.42±0.12）% vs（0.23±0.06）%，（0.32±0.09）%，均P＜0.05]。AngⅡ/BaP复合物组平滑肌细胞凋亡较AngⅡ组及BaP组更明显[（30±12）%vs（19±5）%，（23±4）%，均P＜0.05]。结论 BaP在AngⅡ协同作用下可促进老龄C57BL/6N小鼠形成AAA，其机制可能与BaP通过NF-κB促进MMP-3的表达使弹性纤维紊乱及平滑肌细胞凋亡有关。

Objective To investigate the effect of benzo [a]pyrene （BaP） on the formation of abdominal aortic aneurysm （AAA） in mice and its mechanism. Methods C57BL/6N mice aged 7~9 months were divided into four groups, control group, angiotensinⅡ（AngⅡ） group, BaP group and AngⅡ/BaP group. After 5 weeks of treatment of various agents the abdominal aor-tas of mice were taken. Aortic tissues were subject to HE, immunochemistry staining for evaluation of vascular wal structure, the expression of matrix metal oproteinase- 3, nuclear factor- κB and the apoptosis of vascular smooth muscle cel s. Results AngⅡinfusion with BaP injection induced AAA in 41.67%of mice （versus 25%in AngⅡgroup, P〈0.05）. Histological analysis of the aortic wal showed severe damage to the medial layer and breakage of elastic lamel a. Immunohistochemistry staining showed that the expression of MMP- 3 and NF- κB were increased in AngⅡ/BaP group compared with AngⅡand BaP group （0.48± 0.13%vs 0.24±0.16%and 0.34±0.10%, P〈0.05; 0.42±0.12%vs 0.23±0.06%and 0.32±0.09%, P〈0.05）. The apoptosis of aortic vascular smooth muscle cel s was highest in AngⅡ/BaP group compared with AngⅡand BaP group （30±12%vs 19±5%and 23±4%, P〈0.05）. Conclusion BaP promotes AngⅡ- induced AAA formation in aging C57BL/6N mice, which may be as-sociated with activating NF- κB, up- regulation of MMP- 3 expression, resulting in disarray of elastic lamella, apoptosis of vascu-lar smooth muscle cel s, vascular structural destroy and ultimately aneurysm formation.