【摘要】 目的探讨同型半胱氨酸与胚胎早期心血管发育的关系，了解叶酸和维生素Ｂ１２是否能缓解同型半胱氨酸的心血管发育毒性。方法采用鸡胚孵化、电镜观察、甲基绿派洛宁染色、原位ＤＮＡ片段末端标记、叶酸和维生素Ｂ１２的干预试验等方法。结果同型半胱氨酸（０～１６．０μｍｏｌ／胚胎）能干扰２天和４天龄胚胎心脏发育和血管分化，其作用随着剂量的增加而增强，呈剂量反应关系；８．０μｍｏｌ／胚胎同型半胱氨酸诱发的心脏缺陷率分别为２４．１％和２５．０％，对卵黄囊血管的抑制率达６０７％。≥４．０μｍｏｌ／胚胎同型半胱氨酸能损伤心肌细胞及其细胞器结构，并抑制细胞ＤＮＡ和ＲＮＡ的合成。首次发现８．０μｍｏｌ／胚胎同型半胱氨酸可诱导早期心肌细胞发生过度凋亡（２．７％），明显高于正常对照组（０．０８％）。叶酸能拮抗同型半胱氨酸的心血管毒性，其效果大于维生素Ｂ１２。结论同型半胱氨酸是一种新的能损害心血管发育的危险因素；叶酸能有效地拮抗同型半胱氨酸的发育毒性；细胞凋亡可能与心血管畸形的发生有关。更多还原

【Abstract】 Objective To study the relationship between homocysteine (HCY)and cardiovascular development in the early embryo and to determine whether folic acid and cobalamine(Vit B 12 )can reduce the developmental toxicity of HCY to cardiovascular system.Methods Incubation test for chicken embryo, electron microscopy,methylgreen pyronine stain, in situ fragment end labeling,and intervention trial with folic acid and vitamin B 12 were used in the study.Results Treatment of 0～16.0 μmol of HCY /per embryo could disturb their heart development and differentiation of blood vessels at fetal ages of two and four days,in a dose response pattern,with 24.1% and 25.0% of heart defect and 60.7% of inhibition of blood vessels of yolk sac in 8.0 μmol of HCY,respectively. A dose of more than four μmol/ per embryo could damage the structure of myocardial cells and organelle, and inhibit the synthesis of cellular DNA and RNA. It was the first time to find that 8.0 μmol of HCY could induce excessive apoptosis of myocardial cells(2.7%),significantly higher than that in the normal control group.Folic acid could antagonize the cardiovascular toxicity caused by HCY,stronger than what Vit B 12 could do.Conclusion HCY was a new risk factor which could damage cardiovascular development,and folic acid could effectively antagonize its developmental toxicity.Cellular apoptosis might relate to cardiovascular defect.更多还原