同型半胱氨酸促氧化作用机制探讨  

Research of Mechanism of Homocysteine-induced Oxidative Stress

作　　者：谷兆侠[1] 张俊河[1] 张煜[1] 周延升[1] 

机构地区：[1]新乡医学院生物化学与分子生物学教研室,新乡市453003

出　　处：《医药论坛杂志》2008年第5期16-18,共3页Journal of Medical Forum

摘　　要：目的研究同型半胱氨酸(Hcy)与谷胱甘肽(GSH)和脂质过氧化作用之间的关系,探讨同型半胱氨酸致病作用的机制。方法在体外实验中,以含有谷胱甘肽合成酶系的家兔红细胞裂解液为反应体系,设置对照组和低、高剂量同型半胱氨酸处理组,用荧光法检测反应体系中生成的GSH浓度。在体内实验中,将24只SD大白鼠随机分为3组:对照组,甲硫氨酸处理组和甲硫氨酸加维生素处理组。后两组在饮水中加入一定剂量的甲硫氨酸。此外,甲硫氨酸加维生素组每日灌胃给予维生素B6,B12和叶酸,其余各组给予等量生理盐水。第6周末处死大鼠,分别用高效液相色谱法和荧光法测血浆和肝组织Hcy、GSH和脂质过氧化物(LPO)含量。结果在体外实验中,高、低剂量同型半胱氨酸组的GSH浓度均明显低于对照组(P<0.01),高同型半胱氨酸组比低同型半胱氨酸组降低更明显(P<0.01)。在体内实验中,甲硫氨酸组的血浆Hcy与LPO含量明显高于对照组(P<0.05,P<0.01);给予维生素后,可以抑制Hcy与LPO的升高(P<0.01)。甲硫氨酸组肝匀浆的Hcy含量比对照组增加,而GSH则减少,差异有显著性(P<0.01,P<0.05);甲硫氨酸加维生素组的Hcy含量较甲硫氨酸组明显减少,GSH则明显增加(P<0.01,P<0.05)。结论Hcy可刺激机体的的氧化应激反应,导致体内LPO水平增加,其作用可能与Hcy抑制GSH的合成有关。维生素B6,B12,叶酸的补充,可以抑制Hcy激发的脂质过氧化作用。Objective To investigate the correlation between glutathione, lipid peroxidation and homocysteine, explore the mechanism of atherosclerosis formation induced by homocysteine. Methods In vitro experiment, rabbit erythrocyte lysis solution was prepared for the reactive system containing glutathione synthetase. The experimental samples were divided into three groups：control group, low and high homocysteine groups. Glutathione concentrations formed in the reaction system were measured by fluorometry. In vivo experiment,24 SD rats were randomly divided into three groups： control group, methionine treatment group and methionine ＋ vitamin treatment group. The methionine group and methionine ＋ vitamin group were given drinking water with methionine. In addition, the methionine ＋ vitamin group was given vitamin B6 ,B12 and folic acid by gastrogavage daily,and the other groups were given equal physiological saline. Concentrations of homocysteine in the hepatocyte homogenate and plasma were measured by high performance liquid chromatography, and the glutathione and lipid peroxides were measured by fluorometry, at the end of the sixth week. Results In vitro experiment, compared to the control group, concentrations of glutathione in high and low homocystine groups decreased （P 〈 0. 01 ） ;and it was lower in high homocystine group than that in low homocystenie group （P 〈 0. 01 ） . In vivo experiment, plasma concentrations of homocystine and lipid peroxides were higher （P 〈 0. 05 ,P 〈 0. 01 ） in the methionine group than that in the control group. Hasma levels of homocystine and lipid peroxides in the vitamin ＋ methionine group significantly decreased （P 〈0.01 ）, compared to that of the methionine group. Homocystine concentrations of hepatocyte homogenate were higher （ P 〈 0. 01 ） in methionine group than that of in control group, but glutathione concentrations were lower （P 〈0. 05 ） . In vitamin ＋ methionine group homocystine levels of hepatocyte homogenate significantly decr

关 键 词：同型半胱氨酸 谷胱甘肽 脂质过氧化作用 维生素 甲硫氨酸 

分 类 号：R977.4[医药卫生—药品]