兔饮食所致高同型半胱氨酸血症血管内皮功能的实验研究

目的：观察高同型半胱氨酸血症对血管内皮功能的影响。 方法： 建立兔高同型半胱氨酸血症模型。将18只新西兰兔随机分为：正常对照组（control组）6只、高蛋氨酸饮食组（M组）12只；于实验第4周始，将M组再随机分为两组，M+0组6只，继续饲高蛋氨酸饮食；M+F组6只，在高蛋氨酸饮食基础上，再加以叶酸、VitB12，继续观察3周；6周时统一处死动物，取腹主动脉，制备主动脉血管环，比较M+0组与M+F组及C组主动脉血管对Ach的最大舒张反应。同时，对3组高同型半胱氨酸血症形成过程中0周、3周、6周时血清中Hcy、ET-1、Ang-II、NO2ˉ/NO3ˉ、NOS各指标及处死动物时局部血管组织中ET-1、Ang-II、NO2ˉ/NO3ˉ、NOS指标进行检测并进行比较。 结果： （1）M+0组主动脉血管对Ach的最大舒张反应性(Emax=26.73±4.51)低于M+F组（Emax=47.84±5.62, P<0.05）及control组（Emax=56.42±7.82， P＜0.05）；(2) 3周时，M+0组及M+F组血清中Hcy、ET-1、Ang-II各指标均明显高于对照组及0周时（P＜0.05）；NO2ˉ/NO3ˉ、NOS明显低于对照组及0周时（P＜0.05）；(3)6 周时，M+0组上述指标继续升高；M+F组血清中Hcy低于 M+0组（P＜0.05）;NO2-/NO3-、NOS高于M+0组（P＜0.05）;ET-1、Ang-II各指标与M+F组无明显差异（P>0.05）。 结论： 高同型半胱氨酸血症对血管内皮最大舒张功能具有明显的抑制作用；其机制可能是通过影响局部血管组织内皮细胞 ET-1、Ang-II、NO的分泌而发挥作用的；早期以叶酸、VitB12干预治疗对血管内皮功能具有一定的拮抗作用。

Effect of hyperhomocysteine on endothelial cell function in rabbits

AIM: To investigate the effect of hyperhomocysteine on endothelial cell function. METHODS: By establishing hyperhomocysteinemia model, 18 male New Zealand rabbits were divided into control group (control group) and high-methionine-diet group (M group). At the end of 3 weeks, M group was divided again into M+0 group (continuing high methionine-diet) and M+F group (high-methionine-diet plus folic acid, vitamin B12). At the end of 6 weeks, isolated aortic rings were made and the maximum vasodilation of the aortic rings to Ach was investigated. Meanwhile, the plasma concentrations of Hcy, NO, ET-1, Ang II at 0 week, 3 weeks and 6 weeks and the contents of NO2－/NO3－, Ang Ⅱ, ET-1, NOS in regional vascular tissue at 8 weeks were also measured. RESULTS: (1) In contrast to M+F group and control group, the maximum vasodilation to Ach were decreased (Emax=26.73±4.51 vs 47.84±5.62, 56.42±7.82, P<0.05) in M+0 group. (2) At the end of 3 weeks, the plasma concentration of Hcy, Ang Ⅱ, ET-1 were increased in M group compared with C group and at 0 week (P<0.05), NO and NOS were decreased (P<0.05). (3) At the end of 6 weeks, the plasma concentration of Hcy, Ang Ⅱ, ET-1 were continually increased in M+0 group. In M+F group, by folic acid and vitamin B12 treatment, the level of Hcy was decreased compared with M+0 group (P<0.05). The levels of NO and NOS were increased (P<0.05). However, ET-1, Ang Ⅱ were not obviously changed. CONCLUSIONS: Hyperhomocysteinemia obviously restrains the endothelial vasodilation. The effect is initiated by changing the tissue regional level of ET-1, Ang Ⅱ and NO. By early folic acid and vitamin B12 treatment, the endothelial cell function may be protected.