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

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10-7 mol/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.

Effect of all-trans-retinoic acid on endothelial-dependent dilation in atherosclerosis rabbits

Objective To investigate the effects of all-trans-retinoic acid ( ATRA ) on endothelial-dependent dila-tion in experimental atherosclerosis rabbits. Methods New Zealand white rabbits were randomly divided into 3 groups: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 en-dothelial-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 in-creased significantly (P<0. 05). The concentration of triglyceride(TG) and HDL-C increased significantly after 4 weeks (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 AT-RA 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 -7 mol/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 endo-thelial-dependent dilation decreased, and ATRA might improve endothelium dependent relaxing function by reduc-ing serum lipids.