单硝酸异山梨酯对动脉粥样硬化兔血管内皮细胞功能的影响及机制探讨

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目的研究单硝酸异山梨酯对动脉粥样硬化兔血管内皮细胞功能的影响及机制。方法将30只新西兰大白兔随机分为对照组、高脂组、单硝酸异山梨酯组,每组10只。高脂组给予高胆固醇饲料(1.5%胆固醇+5%猪油的颗粒饲料)喂养,单硝酸异山梨酯组给予高胆固醇饲料+单硝酸异山梨酯0.5 g·kg~(-1)·d~(-1)。8周后,3%戊巴比妥(1 m L·kg~(-1))耳缘静脉注射麻醉,取兔腹主动脉做病理切片,行常规HE染色观察腹主动脉斑块的大小,行免疫组化染色检测植物血凝素样氧化低密度脂蛋白受体-1(LOX-1),P-选择素(P-selectin),并且应用全自动生化分析仪及血生化测定试剂盒,测定动脉硬化兔血清总胆固醇(TC)及三酰甘油(TG)的水平。结果单硝酸异山梨酯组腹主动脉斑块的LOX-1和P-selectin的表达水平明显低于高脂组(P<0.05),但是血清TC、TG与高脂组间差异无统计学意义(P>0.05)。结论单硝酸异山梨酯具有延缓动脉粥样硬化进展的作用,其机制可能与下调LOX-1、P-selectin等黏附分子,减轻斑块炎性细胞浸润进而改善血管内皮细胞功能有关。 Objective To investigate the effect and mechanism of isosorbide mononitrate on the function of vascular endothelial cells in atherosclerotic rabbits. Methods Thirty New Zealand white rabbits were randomly divided into control group, high fat group and isosorbide mononitrate group, with 10 in each group. High cholesterol group was fed with high cholesterol diet (1.5% cholesterol and 5% lard pellet), and the rats in isosorbide mononitrate group were given high cholesterol diet + isosorbide mononitrate 0.5 g · kg -1 · d ~ (-1). After 8 weeks, 3% pentobarbital (1 m L · kg ~ (-1)) was injected into the ear marginalis of the rabbits, and the abdominal aorta was taken for pathological examination. The size of abdominal aortic plaque was observed by routine HE staining. The expression of LOX-1 and P-selectin was detected by immunohistochemical staining. The automatic biochemical analyzer and biochemical assay kit were used to detect the expression of LOX-1, The serum levels of total cholesterol (TC) and triglyceride (TG) in atherosclerotic rabbits were measured. Results The expression of LOX-1 and P-selectin in the abdominal aorta plaques of isosorbide mononitrate group was significantly lower than that of the hyperlipidemia group (P <0.05), but there was no significant difference between the serum TC, TG and high fat group (P> 0.05). Conclusions Isosorbide mononitrate can delay the progress of atherosclerosis. The mechanism may be related to the down-regulation of adhesion molecules such as LOX-1 and P-selectin, alleviation of plaque inflammatory cell infiltration and improvement of vascular endothelial cell function.
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