你可曾無法拒絕下班后的酒宴？你可曾為宿醉而苦惱,？現(xiàn)在,，也許一枚小小的藥片就可以幫你解決所有問題。
9月29日,，據(jù)英國媒體報(bào)道,，澳大利亞研究人員近日在英國《藥物學(xué)》雜志上發(fā)表論文稱，他們正在研制一種能夠使人酒后保持清醒的藥片,，它通過遏制酒精對(duì)大腦的影響幫助解決醉酒的煩惱,。
這種新藥片目前已經(jīng)進(jìn)入小白鼠試驗(yàn)階段，并且取得了很好的效果,。盡管小白鼠被灌了足夠使它們東倒西歪甚至跌到的酒量,，但是由于事先服用了新型藥片，它們并沒有出現(xiàn)醉意,，走路不顯一點(diǎn)踉蹌,。
這一試驗(yàn)結(jié)果幫助科學(xué)家搞清楚了，為什么有些人會(huì)“不勝酒力”——僅幾杯酒下肚后就會(huì)胡言亂語,、神志不清,，甚至失去自我控制力；而另外一些人卻是“海量”——可以神態(tài)自若,、面不改色地連飲數(shù)杯甚至數(shù)瓶,。
研究人員將研究重點(diǎn)放在了占大腦組織90%的神經(jīng)膠質(zhì)細(xì)胞上。神經(jīng)膠質(zhì)細(xì)胞對(duì)免疫系統(tǒng)而言至關(guān)重要,，可以幫助抵抗腦膜炎等感染,。試驗(yàn)顯示，關(guān)停神經(jīng)膠質(zhì)細(xì)胞的免疫反應(yīng)即可防止小白鼠醉酒,。另外還有一個(gè)意外的發(fā)現(xiàn),，即神經(jīng)膠質(zhì)細(xì)胞的免疫功能停止工作的小白鼠比普通小白鼠有著更強(qiáng)的平衡能力。
“小白鼠喝醉和人喝醉很相似,，協(xié)調(diào)性都會(huì)變得很差,。如果阻止了免疫功能，小白鼠就不會(huì)喝醉,，”澳大利亞阿德萊德大學(xué)的研究員馬克·哈欽森介紹說,。
據(jù)了解，這種新型藥片有望在18個(gè)月內(nèi)用于臨床試驗(yàn),，然后3年內(nèi)在柜臺(tái)銷售,。(生物谷 Bioon.com)
doi:10.1111/j.1476-5381.2011.01572.x
PMC:
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.
