大鼠动脉粥样硬化病变各阶段内皮依赖性舒张功能以及亲环素A表达的变化

摘要

Objective: To observe the changes of endothelial-dependent vasodilatation and cyclophilin A (CyPA) expression at different phases of atherosclerosis in experimental rats. Methods: A total of 30 male Wistar rats were divided into 4 groups: Control group, the rats received normal diet, and 3 atherosclerosis groups, the rats received high cholesterol diet for different period of time and a single dose intraperitoneal injection of Vitamin D3 at 600,000 IU/kg, as Atherosclerosis at 8 weeks (AS 8W) group, AS 12W group and AS 15W group, n=8 in each AS group. The rats were sacriifced at the same time to isolate aorta abdominalis. The expression of CyPA at the wall of aorta abdominalis was detected by HE staining and immunohistochemistry. In addition, the aorta abdominalises was cut into 5 mm rings to observe its response to acethylcholine in exvivo organ bath. Results: With prolonged modeling time, the rats at different groups presented normal vessel structure, endothelial cell damage, vessel smooth muscle cell proliferation, atherosclerosis plaque formation and calciifed plaque formation for differentpathological characteristics. The endothelial-dependent vasodilatation was decreased and the maximum vasodilatation percentage in Control group, AS 8W group, AS 12W group and AS 15W group were at (93.46 ± 2.80) %, (82.58 ± 3.25) %, (61.19 ± 3.72)% and (41.28 ± 2.68)% respectively,P<0.05 between each group. The CyPA expression in endothelial cell and vessel smooth muscle cell were increased accordingly in 4 groups by OD value as (0.25 ± 0.06), (0.34 ± 0.09), (0.53 ± 0.09) and (0.68 ± 0.13) respectively,P<0.05 between each group. Conclusion: The CyPA expression increased and the endothelial-dependent vasodilatation decreased with the progress of atherosclerosis accordingly in experimental rats. The expression level of CyPA is related to atherosclerosis degree and it is one of the initial factors for atherosclerosis in rats.%目的：观察高脂饮食喂养大鼠动脉粥样硬化病变各阶段内皮依赖性舒张功能的改变以及亲环素A（CyPA）的表达变化。方法：雄性Wistar大鼠30只随机分为4组，对照组（6只），动脉粥样硬化8周组（AS 8W组）8只，动脉粥样硬化12周组（AS 12W组）8只，动脉粥样硬化15周组（AS 15W组）8只。给予动脉粥样硬化组高脂饲料喂养，并给予维生素D3注射液60万IU/kg一次性腹腔注射，对照组给予基础饲料喂养。同期处死大鼠，分离腹主动脉，行苏木素伊红（HE）染色，免疫组化法检测动脉壁CyPA的表达。另外截取约5 mm新鲜大鼠腹主动脉环，在离体器官浴槽中观察离体腹主动脉环对乙酰胆碱舒张反应。结果：随着造模时间的进展，各组大鼠分别呈现出了血管正常结构、内皮细胞破坏，平滑肌细胞增生、粥样斑块形成以及钙化斑块形成等不同的病变特征。内皮依赖性舒张功能进行性下降，对照组、AS 8W组、AS 12W组、AS 15W组最大舒张度分别为（93.46±2.80）%、（82.58±3.25）%、（61.19±3.72）%、（41.28±2.68）%，各组间差异均有统计学意义（P均＜0.05）。血管内皮细胞以及平滑肌细胞CyPA的表达不断增加，四组大鼠CyPA平均光密度测定分别为0.25±0.06、0.34±0.09、0.53±0.09、0.68±0.13，各组间比较差异均有统计学意义（P均＜0.05）。结论： CyPA的表达随着病变进展不断增加，内皮依赖血管舒张功能进行性下降。CyPA的表达与动脉粥样硬化病变严重程度有关。CyPA可能是动脉粥样硬化的始动因素之一。