巨噬细胞释放基质金属蛋白酶参与尼古丁联合血管紧张素Ⅱ诱导主动脉瘤形成

The involvement of macrophages releasing matrix metalloproteinases in aortic aneurysmal formation induced by nicotine plus angiotensin Ⅱ

目的探讨巨噬细胞释放基质金属蛋白酶(matrix metalloproteinase,MMP)是否参与尼古丁联合血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的腹主动脉瘤形成。方法将10~12个月龄、体重30~33 g的雄性C57BL/6J小鼠随机分为对照组、尼古丁组、AngⅡ组及联合组,分别于皮下灌注生理盐水、尼古丁、AngⅡ、尼古丁+AngⅡ,持续28天后,采用免疫组织化学法分别检测主动脉组织MMP-2、MMP-9及CD68表达。结果与对照组比较,尼古丁组、AngⅡ组、联合组小鼠中膜和外膜MMP-2和MMP-9表达增加,CD68阳性染色细胞定位到主动脉壁的中膜和外膜。联合组小鼠可见中膜断裂,断裂部位出现MMP-2或MMP-9强表达。此外,相邻切片免疫组织化学共定位分析发现:CD68阳性染色位点均出现MMP-2或MMP-9表达,但部分切片表达MMP位置未见CD68阳性染色细胞。结论巨噬细胞分泌MMP-2或MMP-9参与了尼古丁联合AngⅡ诱导主动脉瘤形成。除巨噬细胞外,其他细胞亦有可能分泌MMP-2或MMP-9,具体机制尚待深入探讨。

Objective To explore the involvement of macrophages releasing matrix metalloproteinases（MMPs） in the aortic aneurysms induced by nicotine plus angiotensin Ⅱ（Ang Ⅱ）. Method 10 ~ 12 months old male C57BL/6J mice were treated with nicotine [4 mg/（kg·d）], Ang Ⅱ [0.72 mg/（kg·d）], or both for 28 days. Immunohistochemical analysis was used to examine the expression of MMP-2, MMP-9 and CD68 in aortic tissue. Result Compared with control group, other three treatment groups showed that the expression of MMP-2 and MMP-9 was increased across the aortic media and adventitia,and the CD68 positive cells were detected across the aortic media and adventitia. Nicotine plus Ang Ⅱ induced the stronger expression of MMPs across the broken area of aortic media, but often only one type of MMPs, either MMP-2 or MMP-9. Additionally, the immunohistocheical co-localization analyzation on the contiguous slices showed that CD68 positive sites had the expression of either MMP-2 or MMP-9, not both together, however at some sites expressing MMPs, CD68 positive staining can＇t been detected. Conclusion Macrophages releasing MMP-2 or MMP-9 are involved in the aortic aneurysmal formation induced by nicotine plus Ang Ⅱ, whereas other cells might do so, the mechanism underlying it has yet to be investigated.