安徽医科大学学报

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(P<0.05);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(P<0.05);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(P<0.05)。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(P<0.05),HDL-C浓度4周及12周时明显升高(P<0.05),LDL-C浓度2周及12周时降低(P<0.05);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(P<0.05)。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。

Objective To investigate the effects of all-trans-retinoic acid( ATRA) on endothelial-dependent dilation in experimental atherosclerosis rabbits. Methods New Zealand white rabbits were randomly divided into 3groups: the normal group were fed on standard diet; high-fat diet model group were fed on high-fat diet( standard diet supplemented with 1% cholesterol + 5% lard); ATRA group were fed on high-fat diet and 5 mg/( kg·day)administered orally. After 2,4,8,12 weeks,experimental rabbits were sacrificed to get blood and blood lipids were tested with a kit; the formation of lipid plaque was observed by oil red staining and the change of endothelial structure was watched by HE staining. After 8 weeks,3 rabbits of each group were randomly assigned to detect endothelial-dependent dilation and non-endothelial-dependent dilation on isolated arterial rings. Results Compared with the normal group,after 2 weeks,the concentration of total cholesterol( TCH) and LDL-C in model group increased significantly( P < 0. 05). The concentration of triglyceride( TG) and HDL-C increased significantly after 4weeks( P < 0. 05); Oil red staining showed that in two weeks,lipid plaque was not obvious; 4 weeks later,the lipid plaque was increased; HE staining showed that the intima was thickened with the passage of time; the foam cells increased; the vascular smooth muscle cell polarity was disordered,and migrating to the intima; the change of EDD indicated that the model group attenuated conspicuously( P < 0. 05). Compared with the model group,in ATRA group,there was no difference in the concentration of TG. The concentration of TCH decreased significantly( P< 0. 05); the concentration of HDL-C for 4 weeks and 12 weeks significantly increased( P < 0. 05). The level of LDL-C for 2 weeks and 12 weeks reduced( P < 0. 05); Oil red staining revealed that the lipid plaque was visible after 4 weeks; HE staining indicated that compared with the model group,the intima of ATRA group was slightly thickened,foam cells were reduced,and arrangement of the smooth muscle cells was more neatly; when the level of Ach was 10-7mol/L,the EDD of ATRA group was significantly higher than that in the model group( P <0. 05). Conclusion Hyperlipidemia is a cause of atherosclerosis. The damaged artery endothelium makes endothelial-dependent dilation decreased,and ATRA might improve endothelium dependent relaxing function by reducing serum lipids.