高同型半胱氨酸血症对血管内皮功能及血清可溶性血管细胞黏附分子的影响

Effects of hyperhomocysteinemia on function of endothelium and serum concentration of vascular cell adhesion molecule-1 (VCAM-1)

目的 :通过观察高同型半胱氨酸血症 (HHCY)时兔血浆一氧化氮 (NO)、谷胱甘肽过氧化物酶 (GSH PX)和血管细胞黏附分子 (VCAM 1 )的变化 ,探讨HHCY对内皮功能的影响作用 .方法 :新西兰白兔 1 8只 ,随机分为L 蛋氨酸M组(n =9)和对照N组 (n =9) .分别喂予添加 3%的L 蛋氨酸饲料和普通饲料 ,于 0 ,2 0 ,4 0 ,6 0和 80d检测其血浆中的NO ,GSH PX及VCAM 1的水平 ,同时利用高分辨力超声检测其髂外动脉的内皮依赖性舒张功能 (EDD)、内皮非依赖性舒张功能 (EID) .结果 :HHCY时 ,M组兔髂外动脉的EDD较对照组显著降低 ,0d (1 5 .3± 2 .6 ) % ;2 0d(5 .1± 1 .7) % ;4 0d (2 .7± 1 .0 ) % ;6 0d(- 4 .1± 1 .3) % ;80d(- 5 .5± 1 .3) % ;(P <0 .0 1 ) ,M组的EID亦较对照组明显降低 (P <0 .0 5 ) .其血浆中NO和GSH PX亦较对照组明显降低 (P <0 .0 5 ) ,而血清中VCAM 1较对照组明显升高 ,0d(0 .0 6 6± 0 .0 0 3) μg/L ;2 0d (0 .0 74± 0 .0 0 4 ) μg/L ;4 0d (0 .0 78± 0 .0 0 8)μg/L ;6 0d (0 .0 87± 0 .0 0 8) μg/L ;80d (0 .0 98± 0 .0 1 0 ) μg/L ;(P <0 .0 1 ) .结论 :慢性HHCY兔血浆NO ,GSH PX活性显著下降 ,并使VCAM 1的浓度明显升高 。

AIM: To investigate the effects of hyperhomocysteinemia HHCY on the function of endothelium by observing the changes of NO, ET and the activity of GSH PX and vascular cell adhesion molecule 1 (VCAM 1) in plasma of HHCY rabbits. METHODS: Eighteen New Zealand rabbits were randomized into methionine group(group B, n =9)and control group (group A, n =9). Methionine group was fed with methionine rich diet of L methioine (0.8 g/kg per day) and normal control group was fed with normal diet. The levels of NO, GSH PX in plasma and the serum concentration of VCAM 1 were measured at 20, 40, 60 and 80 d, and endothelium dependent dilation (EDD) and endothelium independent dilation (EID) were examined by high resolution ultrasound. RESULTS: In chronic hyperhomocysteinemia, the EDD of external iliac artery in methioine group was reduced significantly than that in control: 0 d, (15.3±2.6)%, 20 d, (5.1±1.7)%; 40 d, (2.7±1.0)%, 60 d, (-4.1±1.3)% and 80 d, (-5.5±1.3)% ( P < 0.01). The EID in group B was reduced significantly compared with that in group A. The values of plasma in methioine group were markedly higher than those in the control group ( P <0.05) while the levels of NO were lower than those in the control. In methioine group, the serum concentration of VCAM 1 was also significantly higher than that in the control group: 0 d, (0.066±0.003) μg/L, 20 d, (0.074± 0.004) μg/L, 40 d, (0.078±0.008) μg/L, 60 d, (0.087±0.008) μg/L and 80 d, (0.098±0.010) μg/L ( P <0.01). CONCLUSION: Chronic hyperhomocysteinemia leads to endothelia dysfunction in rabbits. EDD is reduced through the inactivation of NO by homocysteinemia and the serum concentration of VCAM 1 is elevated in hyperhomocysteinemia, which is related to the increased oxidative stress and decreased NO level.