血管内皮损伤程度决定动脉硬化斑块的稳定性 缺血再灌注动脉硬化模型的建立

The stability of the atherosclerotic plaque depends on the extent of injured endothelium： results from a novel model of ischemia/reperfusion induced atherosclerosis in carotid artery of rats

目的利用大鼠颈动脉设计一种缺血再灌注的动脉硬化模型，以观察动脉硬化的病理过程及其机制。方法SD大鼠30只，分为正常对照组（对照组）、假手术组和颈总动脉缺血再灌注损伤（IRI）组，每组10只。采用夹闭颈总动脉的方法造成缺血再灌注损伤。4周后苏木精伊红（HE）染色检测新生内膜面积／中膜面积（I／M）值，免疫组织化学法检测新生内膜中血小板内皮细胞黏附分子（CD31）的表达。结果（1）IRI组大鼠血管内膜增生明显，I／M值高于对照组和假手术组（1．328±0．301比0．011±0．004和0．017±0．008，P均〈0．01）。（2）IRI组大鼠血管新生内膜由小到大，从覆盖局部到整个管腔。小的新生内膜相对稳定，而大的新生内膜，病变覆盖整个管腔，呈环状的病变发生自发性断裂，表现不稳定，断裂的新生内膜导致血栓形成。（3）免疫组织化学结果显示，表面覆盖有完整内皮细胞的斑块表现稳定，没有内皮细胞层覆盖的大的斑块表现不稳定。结论大鼠颈动脉缺血再灌注可以形成稳定的动脉硬化模型。血管表面内皮细胞的不完整是动脉硬化斑块破裂的决定因素之一。

Objective To observe the atherogenic lesion progress in a novel ischemia/reperfusion induced atherosclerosis model in the carotid artery of rats. Methods Rats were divided into normal control, sham-operated control and ischemia-reperfusion injury（IRI） groups （n = 10 each ）. IRI was induced by 30 min carotid artery occlusion with a 2 cm long artery clips in anesthetized rats. Four weeks later, hematoxylin and eosin （HE） and immunohistochemical stain were performed on carotid arteries of various groups. The ratio of neointima area/media area （I/M） and expression of platelet endothelial cell adhesion molecule （PECAM-I/CD31） were compared among groups. Results （1） Neointimal hyperplasia was detected in carotid artery of IRI group and the I/M ratio was significantly higher than in normal control and shamoperated groups （ 1. 328 ±0. 301 vs. 0. 011 ±0. 004 and 0. 017 ± 0. 008, all P 〈 0.01 ）. （2） Small to large- sized neointima were found in the IRI group and the small sized intima was stable while large sized intima which covered the whole cavity was instable and underwent spontaneous rupture and thrombosis formation. （3） CD31 expression was significantly upregulated in carotid artery of IRI group corresponding to the instability of neointima in this group. Conclusion Ischemia-reperfusion injury of carotid artery could result in atheroma in rats, this model could be used for future research on the pathogenesis of atherosclerosis. Our results show that endothelium injury of the arteries is the key factor to trigger atheroma and responsible for the disruption of the plaque.