全反式维甲酸对实验性动脉粥样硬化兔动脉血管内皮依赖性舒张功能的影响

发布时间：2018-11-20 05:00

【摘要】：目的探讨全反式维甲酸(ATRA)对实验性动脉粥样硬化兔动脉血管内皮依赖性舒张功能的影响。方法普通级新西兰大耳白兔随机分为3组,正常组:饲喂普通饲料;模型组:饲喂高脂饲料(普通饲料+1%胆固醇+5%猪油);ATRA组:饲喂高脂饲料,同时ATRA灌胃5 mg/(kg·d)。分别于2、4、8、12周后处死取血,检测血清中血脂指标;油红染色观察大体斑块形成情况;HE染色观察动脉的内皮结构变化;8周后,每组随机取3只实验兔进行离体动脉环实验检测兔动脉内皮依赖性舒张功能(EDD)及非内皮依赖性舒张功能(NEDD)。结果与正常组相比,2周后,模型组血清中总胆固醇(TCH)、低密度脂蛋白-胆固醇(LDL-C)浓度显著升高(P0.05);4周后,三酰甘油(TG)、高密度脂蛋白-胆固醇(HDL-C)浓度明显升高(P0.05);油红染色表明2周时脂质斑块不明显,4周以后脂质斑块明显;HE染色显示内膜增厚,泡沫细胞增多,平滑肌细胞极性紊乱,向内膜迁移;内皮依赖性舒张功能高脂组EDD显著低于正常组(P0.05)。与模型组相比,ATRA治疗组血清中TG浓度无差异,TCH浓度明显下降(P0.05),HDL-C浓度4周及12周时明显升高(P0.05),LDL-C浓度2周及12周时降低(P0.05);油红染色表明4周后可见脂质斑块;HE染色显示内膜稍微增厚,泡沫细胞减少,平滑肌细胞排列较整齐;内皮依赖性舒张功能检测表明当乙酰胆碱浓度为10-7mol/L时,ATRA组EDD显著高于高脂组(P0.05)。结论血脂升高可引起动脉粥样硬化的发生,动脉内皮损伤使内皮依赖性舒张功能下降,ATRA可能通过降低血脂改善内皮依赖性舒张功能。
[Abstract]:Objective to investigate the effect of all trans retinoic acid (ATRA) on endothelium-dependent relaxation in experimental atherosclerosis rabbits. Methods New Zealand white rabbits were randomly divided into three groups: normal group: normal diet, model group: high fat diet (1% cholesterol 5% lard); ATRA group was fed with high fat diet and ATRA was given intragastric for 5 mg/ (kg d). After 12 weeks of death, blood samples were collected and blood lipids in serum were detected. The formation of gross plaques was observed by oil red staining. The changes of endothelial structure of arteries were observed by HE staining. After 8 weeks, 3 rabbits in each group were randomly selected for the measurement of endothelium-dependent diastolic function (EDD) and endothelium-independent diastolic function (NEDD).) in isolated rabbit artery rings. Results compared with the normal group, the serum total cholesterol (TCH), low density lipoprotein cholesterol (LDL-C) concentration in the model group was significantly higher than that in the normal group 2 weeks later (P0.05). After 4 weeks, the concentration of triacylglycerol (TG), high density lipoprotein cholesterol (HDL-C) increased significantly (P0.05), oil red staining showed that lipid plaque was not obvious at 2 weeks, but obvious after 4 weeks. HE staining showed that the intima thickened, foam cells increased, smooth muscle cells polarity disorder, migration to the intima; endothelium-dependent diastolic function high fat group EDD was significantly lower than the normal group (P0.05). Compared with the model group, there was no difference in serum TG concentration in ATRA treatment group, TCH concentration decreased significantly (P0.05), HDL-C concentration increased significantly at 4 and 12 weeks (P0.05), and LDL-C concentration decreased at 2 and 12 weeks (P0.05). Oil red staining showed that lipid plaques could be seen after 4 weeks, while HE staining showed that intima thickened slightly, foam cells decreased and smooth muscle cells arranged neatly. Endothelium-dependent diastolic function test showed that EDD in ATRA group was significantly higher than that in hyperlipidemia group when acetylcholine concentration was 10-7mol/L (P0.05). Conclusion elevation of blood lipids may induce atherosclerosis and endothelium injury can decrease endothelium-dependent diastolic function. ATRA may improve endothelium-dependent diastolic function by lowering blood lipid.
【作者单位】：安徽医科大学分子生物学实验室、生物化学与分子生物学教研室、安徽省省部共建教育部重要遗传病基因资源利用重点实验室;
【基金】：国家自然科学基金(编号:81470568)
【分类号】：R543.5

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