子宫内暴露于酒精会损害大脑小动脉的反应性，并增加成年后大脑在缺血/再灌注后损伤的易感性。
In Utero Exposure to Alcohol Impairs Reactivity of Cerebral Arterioles and Increases Susceptibility of the Brain to Damage Following Ischemia/Reperfusion in Adulthood.
机构信息
Department of Molecular Biology , University of Texas-Southwestern, Dallas, Texas.
Division of Basic Biomedical Sciences , Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota.
出版信息
Alcohol Clin Exp Res. 2019 Apr;43(4):607-616. doi: 10.1111/acer.13979. Epub 2019 Mar 7.
BACKGROUND
Maternal consumption of alcohol produces abnormalities in the developing fetus and can contribute to an increased incidence of many cardiovascular-related diseases. The first goal of this study was to determine whether in utero exposure to alcohol influences reactivity of cerebral arterioles in adult (12 to 15 weeks old) rats. The second goal of this study was to examine whether in utero exposure to alcohol increased the susceptibility of the brain to damage following an ischemic event in adult rats.
METHODS
We fed Sprague Dawley dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy (21 to 23 days). In the first series of studies, we examined reactivity of cerebral arterioles to endothelial nitric oxide synthase (eNOS)- (adenosine diphosphate [ADP]) and neuronal nitric oxide synthase (nNOS)-dependent N-methyl-D-aspartate (NMDA, and NOS-independent agonists in adult rats before and during application of l-NMMA. In another series of studies, we examined infarct volume following middle cerebral artery occlusion in adult offspring exposed to alcohol in utero. In both series of studies, we also determined the role for an increase in oxidative stress by feeding dams apocynin for the duration of their pregnancy.
RESULTS
We found that in utero exposure to alcohol reduced responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in adult rats. In addition, treatment of the dams with apocynin prevented this impairment in cerebral vascular function. We also found that in utero exposure to alcohol worsened brain damage following ischemia/reperfusion in adult rats and that treatment of dams with apocynin prevented this increase in brain damage following ischemia/reperfusion.
CONCLUSIONS
We suggest that our findings may have important implications for the pathogenesis of brain abnormalities associated with fetal alcohol exposure.
背景
母体摄入酒精会导致胎儿发育异常，并可能导致许多心血管相关疾病的发病率增加。本研究的首要目标是确定胎儿期暴露于酒精是否会影响成年（12 至 15 周龄）大鼠大脑小动脉的反应性。本研究的第二个目标是检查胎儿期暴露于酒精是否会增加成年大鼠在缺血事件后大脑易受损伤的敏感性。
方法
我们在妊娠期间（21 至 23 天）用含或不含酒精（3%乙醇）的液体饮食喂养 Sprague Dawley 孕鼠。在第一项研究系列中，我们在成年大鼠中应用 l-NMMA 之前和期间，研究了大脑小动脉对内皮型一氧化氮合酶（eNOS）-（二磷酸腺苷 [ADP]）和神经元型一氧化氮合酶（nNOS）依赖性 N-甲基-D-天冬氨酸（NMDA）的反应性，以及一氧化氮合酶非依赖性激动剂。在另一项研究系列中，我们在胎儿期暴露于酒精的成年后代中检查了大脑中动脉闭塞后的梗死体积。在这两项研究系列中，我们还通过在妊娠期间给孕鼠喂食 apocynin 来确定氧化应激增加的作用。
结果
我们发现，胎儿期暴露于酒精会降低成年大鼠大脑小动脉对 ADP 和 NMDA 的反应，但对硝化甘油无影响。此外，apocynin 处理孕鼠可预防这种脑血管功能障碍。我们还发现，胎儿期暴露于酒精会加重成年大鼠缺血再灌注后的脑损伤，而 apocynin 处理孕鼠可预防缺血再灌注后脑损伤的增加。
结论
我们认为，我们的发现可能对与胎儿酒精暴露相关的脑异常的发病机制具有重要意义。
Zotero 插件