同型半胱氨酸对谷胱甘肽合成影响及致病作用
Effect of homocysteine on glutathione synthesis and mechanism of causing disease
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摘要:目的 研究同型半胱氨酸对谷胱甘肽合成的影响, 探讨同型半胱氮酸致动脉粥样硬化机制。方法 在体外实验中, 以鼠红细胞裂解液为反应体系, 分别检测对照组和低、高剂量同型半胱氨酸处理后反应体系中生成的无机磷酸和谷胱甘肽含量, 以生成的无机磷酸的mmol数表示γ-谷氨酰半胱氨酸合成酶的活性。在体内实验中, 将大鼠随机分为对照组, 高、低剂量蛋氨酸处理组和蛋氨酸+维生素处理组, 分别测定血浆谷胱甘肽含量。结果 与对照组比较, 高、低剂量同型半胱氨酸组的无机磷酸生成量均明显降低(P < 0.01), 谷胱甘肽的含量也显著减少(P < 0.01)。与对照组比较, 高剂量蛋氨酸处理组的谷胱甘肽生成量明显降低(P < 0.01);蛋氨酸+维生素处理组的谷胱甘肽含量与对照组相比, 差异无统计学意义(P > 0.05), 但比高蛋氨酸组明显增多(P < 0.01)。结论 同型半胱氨酸的存在能明显抑制谷胱甘肽的合成, 其作用与同型半胱氨酸对γ-谷氨酰半胱氨酸合成酶的抑制有关。这可能是同型半胱氨酸致动脉粥样硬化的主要机制之一。Abstract:Objective To investigate the effect of homocysteine on glutathione synthesis and the relation between homocysteine and atherosclerosis formation.Methods In vitro experiment, rater ythrocytelysing solution was prepared for the reactive system.The contents of phosphate and glutathione formed in the reaction system were respectively measured in control group, low and high homocysteine treatment groups.The activity of C-glutamylcysteine synthetase was showed by the content of inorganic phosphate formed in the reaction.In vivo experiment, The content of rat plasma glutathione was measured in control group, low and high dosage mathionine treatment groups.Results The phosphate contents in high and low homocystine groups were significantly decreased compared with the control group(P < 0.01).The contents of glutathione in high and low homocysteine groups were lower than the control group(P < 0.01)The content of glutathione in high mathionine group was significantly lower than that of control group(P < 0.01), There was no notable difference in content of glutathio ne between vitamin+mathionine and control group(P > 0.05), but the content of glutathione in vitamin+mathio nine group was significantly raised compared with high mathionine group(P < 0.01).Conclusion Homocysteine has a significant inhibitive effect on glutathione synthesis, which is correlative with the inhibition of homocysteine on C-glutamylcysteine synthetase.This is probably one of the main mechanisms of the rosclerosis formation induced by homocysteine.
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