2018 年第 12 期 第 13 卷

叶酸和维生素B6及维生素B12缺乏对脑梗死大鼠甲基代谢及认知功能的影响

Effect of folic acid, vitamin B6 and B12 deficiency on methylation metabolism and cognitive function in cerebral infarction rats

作者：张煜伟张赛涂悦王海生王振国刘洋

英文作者：

单位：300162天津，武装警察部队后勤学院附属医院急诊科(张煜伟)，脑科中心(张赛、涂悦)，营养科（王海生），医教部（王振国）；200081上海市第四人民医院神经内科(刘洋）

英文单位：

关键词：脑梗死；叶酸；维生素B6；维生素B12；DNA甲基化

英文关键词：

• 摘要：

• 【摘要】目的    探究叶酸和维生素B6及维生素B12缺乏对大脑中动脉栓塞（MCAO）模型大鼠甲基代谢及认知功能的影响。方法    将26只MCAO模型大鼠按随机数字表法分为Diet组和Ctrl组，各13只。Diet组喂食叶酸、维生素B6和维生素B12缺乏饲料；Ctrl组喂食对照饲料，喂养时间为6周。采用高效液相色谱法检测血浆中甲基代谢产物同型半胱氨酸（Hcy）、S-腺苷甲硫氨酸(SAM)、S-腺苷同型半胱氨酸（SAH）的含量。采用DNA总甲基化定量检测试剂盒检测脑组织DNA总甲基化水平。采用Morris水迷宫实验检测大鼠认知功能。结果    与Ctrl组相比，Diet组血浆Hcy、SAH浓度升高［（36±9）μmol/L比（14±4）μmol/L、（13.9±1.5）μmol/L比（8.8±1.9）μmol/L］，血浆SAM浓度降低［（10.4±2.0）μmol/L比（16.7±1.7）μmol/L］，DNA总甲基化水平降低［（0.47±0.03）%比（0.62±0.04）%］，第3、4、5天定向航行实验平均逃避潜伏期时间增加［（51±9）s比（32±7）s、（47±8）s比（30±7）s、（45±8）s比（25±9）s］，学习记忆能力和空间探索能力下降，差异均有统计学意义(均P＜0.05)。结论    叶酸、维生素B6和维生素B12缺乏可导致MCAO模型大鼠Hcy水平升高、DNA甲基化水平下降及认知功能损害。

• 【Abstract】Objective    To investigate the effect of folic acid, vitamin B6 and B12 deficiency on methylation metabolism and cognitive function in middle cerebral artery occlusion(MCAO) model rats. Methods    Twenty-six MCAO model rats were randomly divided into Diet group treated with folic acid, vitamin B6 and B12 deficiency feedstuff and control group（Ctrl group）, with 13 rats in each group. The rats were fed for 6 weeks. Methyl metabolites including homocysteine(Hcy), S-adenosylmethionine(SAM) and S-adenosinehomocysteine(SAH) in plasma were tested by high performance liquid chromatography. DNA methylation in brain tissue was tested by methylation quantitative detection kit. Cognitive function of rats was assessed by Morris water maze test. Results    In the Diet group, plasma concentrations of Hcy and SAH were higher［（36±9）μmol/L vs （14±4）μmol/L, （13.9±1.5）μmol/L vs （8.8±1.9）μmol/L］, SAM concentration was lower［（10.4±2.0）μmol/L vs （16.7±1.7）μmol/L］ and DNA methylation level was lower［（0.47±0.03）% vs （0.62±0.04）%］ than those in the Ctrl group(all P＜0.05). Escape latencies in the Diet group were longer than those in the Ctrl group on the 3rd, 4th, 5th day of Morris test［（51±9）s vs （32±7）s, （47±8）s vs （30±7）s, （45±8）s vs （25±9）s］; learning, memory and space exploration capability of rats in the Diet group were poorer than those in the Ctrl group(all P＜0.05). Conclusion    Deficiency of folic acid, vitamin B6 and B12 can cause Hcy increase, DNA methylation decline and cognitive function impairment in MCAO rats.