你可曾无法拒绝下班后的酒宴？你可曾为宿醉而苦恼？现在，也许一枚小小的药片就可以帮你解决所有问题。
9月29日，据英国媒体报道，澳大利亚研究人员近日在英国《药物学》杂志上发表论文称，他们正在研制一种能够使人酒后保持清醒的药片，它通过遏制酒精对大脑的影响帮助解决醉酒的烦恼。
这种新药片目前已经进入小白鼠试验阶段，并且取得了很好的效果。尽管小白鼠被灌了足够使它们东倒西歪甚至跌到的酒量，但是由于事先服用了新型药片，它们并没有出现醉意，走路不显一点踉跄。
这一试验结果帮助科学家搞清楚了，为什么有些人会“不胜酒力”——仅几杯酒下肚后就会胡言乱语、神志不清，甚至失去自我控制力；而另外一些人却是“海量”——可以神态自若、面不改色地连饮数杯甚至数瓶。
研究人员将研究重点放在了占大脑组织90%的神经胶质细胞上。神经胶质细胞对免疫系统而言至关重要，可以帮助抵抗脑膜炎等感染。试验显示，关停神经胶质细胞的免疫反应即可防止小白鼠醉酒。另外还有一个意外的发现，即神经胶质细胞的免疫功能停止工作的小白鼠比普通小白鼠有着更强的平衡能力。
“小白鼠喝醉和人喝醉很相似，协调性都会变得很差。如果阻止了免疫功能，小白鼠就不会喝醉，”澳大利亚阿德莱德大学的研究员马克·哈钦森介绍说。
据了解，这种新型药片有望在18个月内用于临床试验，然后3年内在柜台销售。(生物谷 Bioon.com)
doi:10.1111/j.1476-5381.2011.01572.x
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PMID:
Inhibiting the TLR4-MyD88 signalling cascade by genetic or pharmacologic strategies reduces acute alcohol dose-induced sedation and motor impairment in mice
Yue Wu1, Erin L. Lousberg, Lachlan M. Moldenhauer, John D. Hayball, Janet K. Coller, Kenner C. Rice, Linda R. Watkins, Andrew A. Somogyi, Mark R. Hutchinson
Summary
BACKGROUND AND PURPOSE Emerging evidence implicates a role for toll-like receptor 4 (TLR4) in the central nervous system effects of alcohol. The current study aimed to determine whether TLR4-MyD88-dependent signalling was involved in the acute behavioural actions of alcohol and if alcohol could activate TLR4-downstream MAPK and NFκB pathways.
EXPERIMENTAL APPROACH The TLR4 pathway was evaluated using the TLR4 antagonist (+)-naloxone (µ-opioid receptor-inactive isomer) and mice with null mutations in the TLR4 and MyD88 genes. Sedation and motor impairment induced by a single dose of alcohol were assessed by loss of righting reflex (LORR) and rotarod tests, separately. The phosphorylation of JNK, ERK, and p38, and levels of IκBα were measured to determine the effects of acute alcohol exposure on MAPK and NFκB signalling.
KEY RESULTS After a single dose of alcohol, both pharmacological inhibition of TLR4 signalling with (+)-naloxone and genetic deficiency of TLR4 or MyD88 significantly (p < 0.0001) reduced the duration of LORR by 45-78%, and significantly (p < 0.05) decreased motor impairment recovery time to 62-88% of controls. These behavioural actions were not due to changes in the peripheral or central alcohol pharmacokinetics. IκBα levels responded to alcohol by 30 min in mixed hippocampal cell samples, from wild-type mice, but not in cells from TLR4 or MyD88 deficient mice.
CONCLUSIONS AND IMPLICATIONS These data provide new evidence that TLR4-MyD88 signalling is involved in the acute behavioural actions of alcohol in mice.
