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同型半胱氨酸对鸡胚早期心血管发育的影响 |
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李勇 李竹 陈星 齐佩文 李松
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（0～16.0 μmol/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；8.0 μmol/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％。≥4.0 μmol/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8.0 μmol/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。
关键词 半胱氨酸 心血管畸形 叶酸 脱噬作用
Effects of Homocysteine on Cardiovascular Development in Early Chicken Embryo
LI Yong，LI Zhu，CHEN Xing，et al．
National Center for Maternal and Infant Health Care of China, Beijing Medical University，Beijing 100083
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 B12）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 B12 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 B12 could d[1] [2] 下一页
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