酒精对小鼠胚胎脑线粒体发育的影响

目的探讨孕期酒精染毒对后代脑线粒体发育的影响。方法ICR孕鼠随机分成3个酒精染毒组和一个空白对照组,染毒期为孕6～15天,孕18天剖腹取胎,提取胎鼠脑线粒体,测定线粒体膜电位、呼吸酶活性、ATP合成酶活性和线粒体内ATP含量。结果随着酒精染毒剂量的增高,胎鼠头体重比逐渐降低,中、高剂量组出现小头畸形;流式细胞检测显示胚胎脑线粒体幼稚群的比例逐渐增多,由对照组的18%上升到34%;在中、高剂量组呼吸酶复合体Ⅰ和Ⅳ的活性均较对照显著降低,30g(kg·d)染毒组分别相当于对照的917%和879%,60g(kg·d)染毒组分别相当于对照的724%and697%,呈剂量反应关系;60g(kg·d)染毒组胎鼠脑线粒体ATP合成酶的活性较对照显著降低,相当于对照的803%;30g(kg·d)和60g(kg·d)染毒组胎鼠脑线粒体内ATP的含量均较对照组显著降低。结论孕期酒精染毒能够影响胚胎脑线粒体的发育和功能成熟,可能与酒精所致神经管畸形有关。

Effect of alcohol on brain mitochondria development of mouse embryos

OBJECTIVE: To probe the effect of alcohol consumption on brain mitochondria development of mouse embryos. METHODS: Pregnant mice were given alcohol intragastrically from pregnant day (PD) 6 - 5. On PD 18, embryos were dissected out and the brain mitochondria were extracted. Then mitochondria membrane potential, activities of mitochondria respiratory chain complex I, IV and ATPase, and ATP content were measured in vitro. RESULTS: The ratio of fetal brain/body weight decreased as the maternal alcohol dosage increasing. An increased proportion of immature mitochondria, from 18 percent to 34 percent, was detected by flow cytometry. Reduced activities of respiratory chain complexes I and IV were found in 3.0 g/kg/day (91.7% and 87.9% respectively) and 6.0 g/kg/day alcohol exposure groups (72.4% and 69.7% respectively). Only 6.0 g/kg/day ethanol exposure group showed significantly reduced activity (80.3% of control) of ATPase. ATP contents in the fetal brain mitochondria of 3.0 g/kg/day and 6.0 g/kg/day maternal alcohol exposure groups were significantly less than that of control, implying an impaired mechanism of ATP synthesis and/ or uptake. CONCLUSION: Alcohol consumption during pregnancy can affect embryo brain mitochondria development, which may be related to the neural tube defects induced by alcohol.