睡眠呼吸暂停综合征致高脂饮食老年大鼠动脉粥样硬化的研究

Effect of sleep apnea syndrome on atherosclerosis of cholesterol-fed old rat

目的探讨睡眠呼吸暂停综合征对动脉粥样硬化(AS)早期老年大鼠动脉平滑肌细胞增生及细胞间黏附分子(ICAM-1)表达的影响。方法选取Wistar雄性青年大鼠〔3月龄,体重(250±30)g〕与老年大鼠〔20月龄,体重(450±50)g〕各24只。各组随机分为对照组、高脂组及缺氧组,每组8只。实验时间12周,实验终点电镜观察胸主动脉内皮平滑肌细胞的特征、免疫细胞化学方法评价AS早期大鼠动脉增殖细胞核抗原(PCNA)及ICAM-1蛋白表达的改变。结果(1)高脂组与缺氧组均出现高脂血症。(2)高脂组出现轻度内皮损伤,老年缺氧组内皮病理损伤较高脂组严重,形成典型的AS早期病变,包括内皮细胞脱失,平滑肌细胞增殖、迁移,吞噬脂质空泡等。(3)高脂组动脉内膜PCNA及ICAM-1蛋白表达积分光密度值均显著增加,缺氧组较高脂组血管壁PCNA及ICAM-1蛋白表达水平明显升高(P<0.01),老年高脂组及缺氧组较相同条件青年组PCNA及ICAM-1表达均显著增高(P<0.01)。结论睡眠呼吸暂停综合征可加速高脂血症大鼠AS早期病变的进程,其机制可能与缺氧诱导的动脉内皮ICAM-1蛋白表达增加,促进动脉平滑肌细胞增殖有关,从而可能在AS发生发展过程中起重要作用。

Objective To investigate effects of sleep apnea syndrome on expression of intercellular adhesion molecule-1 （ICAM-1） and proliferation cell nuclear antigen （PCNA） in a cholesterol-fed rat model of early atherosclerosis. Methods Twenty-four male young Wistar rats[3 months old, （250±30]gland twenty-four senile Wistar rats [20 months old, （450±50）g] were randomly divided into 3 groups （n=8）. The first group was fed with normal diet as blank control, the second group was fed with high cholesterol diet as cholesterol-fed control group,the third group was fed with high cholesterol diet and got simulated sleep apnea syndrome by chronic intermittent hypoxia exposure. The thoracic aorta was examined by electron microscopy at the end of experiment. Expression of PCNA and ICAM-1 protein on artery endotheliocyte were detected by immunohistochemistry. Results （1） Rats of both groups 2 and 3 showed hyperlipemia. Statistical analysis showed an obvious difference as compared with blank control group（P〈0.01）. （2）Mild lesion of arterial endothelium was observed in the cholesterol-fed groups. The typical early lesion of atherosclerosis was observed only in the group （3）The changes included significant endothelial exfoliation, proliferation and migration of smooth muscle cells, accumulation of lipid and cholesterol in the cells. 3. The expression of PCNA and ICAM-1 protein in sleep apnea syndrome group was singnificantly increased as compared with control group （P〈0.01）. Conclusion Sleep apnea syndrome caused by chronic intermittent hypoxia exposure induces typical thoracic aorta atherosclerosis, vascular ICAM-1 expression and smooth muscle cells proliferation in the cholesterolfed rats.