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口服乳果糖通过氢气治疗脑缺血再灌注损伤

已有 3734 次阅读 2013-8-17 21:02 |个人分类:诱导氢气|系统分类:论文交流

乳果糖在临床上被用于便秘和肝性脑病的治疗,由于乳果糖不能在小肠内吸收,进入大肠被细菌利用可以产生氢气,氢气可以在大肠被吸收,氢气被证明可以治疗包括脑缺血在内的许多炎症和氧化损伤相关疾病。

乳果糖在结肠中被消化道菌丛转化成低分子量有机酸,导致肠道内pH值下降,并通过渗透作用增加结肠内容量。上述作用刺激结肠蠕动,保持大便通畅,缓解便秘,同时恢复结肠的生理节律。

我们的观点认为,乳果糖促进大肠细菌产生氢气可能使该药物治疗脑病的原因,当然为了证明这个观点,我们采用脑缺血模型,并从氢气可以诱导内源性抗氧化系统角度进行系列分析。该文章目前在线发表在Free RadicalBiology and Medicine

该文章仍存在一些缺陷,例如乳果糖促进大肠细菌产生的物质不只是氢气,也可能有甲烷、硫化氢和小分子有机酸(脂肪酸)。这些物质是否也是一种因素值得关注,而且从道理上讲,如果要证明氢气是肝性脑病的治疗机制,也应该考虑氢气对氨中毒引起的脑功能损伤是否有直接的对抗作用。这些问题仍值得深入研究和探讨。最近有研究发现,大肠内细菌产生的脂肪酸是诱导Treg细胞的重要介质,那么这种效应也应该考虑。如果长期口服这种药物,大肠内细菌的类型是否会受到影响,这都是很重要的问题。 

Lactulose amelioratescerebral ischemia-reperfusion injury in rats through inducing hydrogen viaactivating Nrf2 expression

 

Molecularhydrogen has been proved effective in ameliorating cerebral ischemia/reperfusion(I/R) injury by selectively neutralizing reactive oxygen species. Lactulose canproduce considerable amount of hydrogen through fermentation by the bacteria inthe gastrointestinal tract. To determine the neuroprotective effects oflactulose against cerebral I/R injury in rats and explore the probablemechanisms, we carried out this study. The stroke model was produced onSprague-Dawley(SD) rats through middle cerebral artery occlusion(MCAO).Intragastric administration of lactulose substantially increased hydrogenbreath concentration. Behavioral and histopathological verifications matchedbiochemical findings. Behaviorally, rats in lactulose administration group wonhigher neurological scores and showed shorter escape latency time in Morris test.Morphologically, 2,3,5-triphenyltetrazolium chloride (TTC) showed smallerinfarction volume; Nissl staining manifested relatively clear and intactneurons and TUNEL staining showed less apoptotic neurons. Biochemically,lactulose decreased brain malondialdehyde(MDA) content, caspase-3 activity,3-nitrotyrosine(3-NT) and 8-hydroxy-2-deoxyguanosine(8-OHdG) concentration andincreased superoxide dismutase(SOD) activity. And the effects of lactulose weresuperior to edaravone. Lactulose orally administered activated the expressionof NF-E2-related factor 2(Nrf2) in the brain verified by RT-PCR and Westernblot. The antibiotics suppressed the neuroprotective effects of lactulose viareducing hydrogen production. Our study for the first time demonstrated a noveltherapeutic effect of lactulose on cerebral ischemia/reperfusion injury and theprobable underlying mechanisms. Lactulose intragastrically administeredpossessed neuroprotective effects on cerebral I/R injury in rats, which couldbe attributed to hydrogen production by the fermentation of lactulose throughintestinal bacteria and Nrf2 activation.



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