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PNAS:研究揭示酒精成瘾机制

来源:中国科学报 2013-12-13 17:40

来自中国科学院武汉物理与数学研究所徐富强课题组的一项最新研究成果,直观地揭示了酒精作为能源物质直接参与大脑的代谢过程,部分解释了酒精成瘾机制。相关论文日前发表于美国《国家科学院院刊》。

据论文第一作者、课题组成员、副研究员王杰介绍,进入体内的酒精,约10%通过呼吸和体液被排出体外,其余90%经过肝脏转化为醋酸盐,成为可被利用的能源物质。近年来,在人体和动物上的研究表明,长期饮酒或酒精成瘾可明显地降低大脑葡萄糖的代谢速率。但大脑能否利用酒精及其代谢物作为能源物质、大脑内醋酸盐类的来源等都是悬而未决的问题。

研究人员通过与美国耶鲁大学核磁共振研究中心合作,利用磁共振可见的分子探针跟踪酒精在生物体内的代谢行为。通过自主研发设计的酒精蒸气室设备,研究人员为大鼠提供了一个稳定的酒精蒸气环境,建立了一个长期“酗酒”的动物模型,进而对长期“饮酒”大鼠的大脑代谢行为进行了观测。

研究结果表明,通过连续三周的“酗酒”训练,大鼠大脑内醋酸盐类物质的代谢结果并未发生显著的变化,然而酒精的代谢速率却有了显著性的提高,尤其是在大脑皮层。

“酒精代谢速率的提高,是部分取代了葡萄糖作为能源,还是生理病理导致葡萄糖的代谢速率降低,还是兼而有之,目前还在研究中。”王杰认为,相对于其他的能源物质,酒精在胶质细胞内参与代谢行为的比例明显升高,这些研究结果从能量代谢的角度为研究酒精成瘾的发病机理提供了生物化学基础,为研发抗酒精成瘾药物提供了新角度。(生物谷Bioon.com)

生物谷推荐的英文摘要

Proceedings of the National Academy of the Sciences                doi: 10.1073/pnas.1306011110

Oxidation of ethanol in the rat brain and effects associated with chronic ethanol exposure

Jie Wanga,b, Hongying Dub,c, Lihong Jiangb, Xiaoxian Mab, Robin A. de Graafb, Kevin L. Behard, and Graeme F. Masonb,d,1

It has been reported that chronic and acute alcohol exposure decreases cerebral glucose metabolism and increases acetate oxidation. However, it remains unknown how much ethanol the living brain can oxidize directly and whether such a process would be affected by alcohol exposure. The questions have implications for reward, oxidative damage, and long-term adaptation to drinking. One group of adult male Sprague–Dawley rats was treated with ethanol vapor and the other given room air. After 3 wk the rats received i.v. [2-13C]ethanol and [1, 2-13C2]acetate for 2 h, and then the brain was fixed, removed, and divided into neocortex and subcortical tissues for measurement of 13C isotopic labeling of glutamate and glutamine by magnetic resonance spectroscopy. Ethanol oxidation was seen to occur both in the cortex and the subcortex. In ethanol-nave rats, cortical oxidation of ethanol occurred at rates of 0.017 ± 0.002 μmol/min/g in astroglia and 0.014 ± 0.003 μmol/min/g in neurons, and chronic alcohol exposure increased the astroglial ethanol oxidation to 0.028 ± 0.002 μmol/min/g (P = 0.001) with an insignificant effect on neuronal ethanol oxidation. Compared with published rates of overall oxidative metabolism in astroglia and neurons, ethanol provided 12.3 ± 1.4% of cortical astroglial oxidation in ethanol-nave rats and 20.2 ± 1.5% in ethanol-treated rats. For cortical astroglia and neurons combined, the ethanol oxidation for nave and treated rats was 3.2 ± 0.3% and 3.8 ± 0.2% of total oxidation, respectively. 13C labeling from subcortical oxidation of ethanol was similar to that seen in cortex but was not affected by chronic ethanol exposure.

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