外膜炎症诱发载脂蛋白E基因敲除鼠冠状动脉粥样硬化病灶

研究载脂蛋白E基因敲除(载脂蛋白E°)小鼠冠状动脉内粥样硬化病灶的分布、组成与动脉外膜炎症的关系.取载脂蛋白E°小鼠心脏作连续切片,Movat法染色,追踪冠状动脉主干及其心肌内的小分支;寻找病灶,观察病灶内组成,分析其分布规律.复制小鼠股动脉外膜无菌性炎症模型,用免疫组织化学方法检查内膜粘附分子的表达.结果发现,冠状动脉主干内有延伸病灶,在主干以下分支(包括心肌内小分支)内有在原位生成的病灶,在两类病灶相邻的外膜有炎性细胞浸润,外膜炎症面积大于动脉粥样硬化病灶累及的内膜面积,亦发现一些部位血管外有炎性细胞浸润,而尚无病灶形成.原位病灶均发生于心室壁,大的原位病灶多发生在左室壁心肌内、血管分支处和乳头肌附近的冠状动脉分支内.股动脉外膜炎症可诱发内膜表达细胞间粘附分子1和血管细胞粘附分子1,同时伴白细胞的附壁.以上提示血管外膜炎症是小鼠冠状动脉内病灶的一个始动环节.

Adventitial Inflammation Induces the Formation and Progress of the Atherosclerotic Lesions within Coronary Artery of ApoE Knockout Mice

Aim To observe the occurrence and the morphological manifestation of atherosclerotic lesions in apolipoprotein E gene knockout (ApoE -/-) mice. Explore the relationship between lesion formation and adventitial inflammation. Methods The successive sections of the hearts of 60 and 112 weeks old ApoE -/- mice were made, then stained by Movat method. Trailled all the trunks and intra-myocardial small branches of coronary arteries for finding the lesions, and analyzed the relationship between lesion distribution and adventitial inflammation. The aseptic adventitial inflammation of the femoral artery in C57BL/6 mice were duplicated, detected the expression of adhesive molecules. Results There were extending lesions in the trunks of coronary artery, which extended directly from the aorta. There were in situ lesions in the branches of the trunks (including intra-myocardial small branches). There were inflammatory cells aggregation at the adventitia with the lesions at the corresponding intima. The infiltrating area of inflammatory cells was much larger than the area of lesion at intima. Some positions with inflammatory infiltration in adventitia could be seen without lesion at corresponding intima. All the in situ lesions were arised within ventricular muscle, most of the large in situ lesions appeared in the left ventricular wall. ICAM-1, VCAM-1 and adhesion of white blood cells could be seen at the intima of femoral artery in the mice with experimental aseptic adventitial inflammation. Conclusions The adventitial inflammation is one of the predisposing factors for the formation of lesions within the coronary artery.