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氢气对脑缺血再灌注损伤的治疗作用早就有许多报道,保护呼吸氢气和注射氢气生理盐水,但脑缺血再灌注并不能代表所有的脑缺血类型,临床上许多的脑缺血并不会有再灌注,因此对持续性局部脑缺血是否具有治疗作用,仍是需要回答的问题。最近来自第四具有大学西京医院麻醉科和天津大学附属医院麻醉科的一项研究针对这一问题进行探讨。
他们采用大鼠局灶持续性脑缺血模型,分别于缺血后不同时间注射不同剂量的氢气生理盐水,结果发现,尽管氢气生理盐水对局部脑血流没有产生任何影响,但对脑梗死体积和神经功能均有明显的改善作用,这种作用存在剂量依赖关系。同时对脑组织的炎症因子、抗氧化酶和氧化损伤指标产生显著影响,可以降低炎症因子,提高组织保护氧化损伤的能力、降低组织氧化损伤。研究结果提示,氢气作为一种良好的抗氧化物质,不仅对脑缺血再灌注损伤,而且对持续性缺血都可以具有治疗作用。另外,氢气对脑实质出血、蛛网膜下腔出血都具有治疗作用,临床证据发现对脑干梗死具有治疗价值,如果上述这些研究结果能获得临床研究的支持,那么氢气作为一种广谱的各种类型脑血管疾病的治疗手段,将具有非常巨大的临床应用潜力。
不过这种美好愿望也要考虑到治疗时机,即使从动物模型角度,目前仍不清楚当治疗时间延迟后,是否仍具有治疗价值。例如我们的研究都是在缺血非常早期使用氢气,但临床患者大部分都在缺血一定时间后才可以获得干预手段,而对时间比较长,脑组织坏死到一定程度,再进行干预,到底是否仍有作用,是非常令人怀疑的。
Protective effects of hydrogen-rich saline in a rat model of permanent focal cerebral ischemia via reducing oxidative stress and inflammatory cytokines ☆
Jianjun Li1,
Department of Neurology, No. 323 Hospital of PLA, Xi’an 710054, Shaanxi Province, P. R. China
Hydrogen gas (H2) as a new medical gas exerts organ-protective effects through regulating oxidative stress, inflammation and apoptosis. In contrast to H2, hydrogen-rich saline (HS) may be more suitable for clinical application. The present study was designed to investigate whether HS can offer a neuroprotective effect in a rat model of permanent focal cerebral ischemia and what mechanism(s) underlies the effect. Sprague-Dawley rats were subjected to permanent focal cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAO). Different doses of HS or normal saline were intraperitoneally administered at 5 min after pMCAO or sham operation followed by injections at 6 h, 12 h and 24 h. Here, we found that HS treatment significantly reduced infarct volume and improved neurobehavioral outcomes at 24 h, 48 h and 72 h after pMCAO operation in a dose-dependent manner (P<0.05). Moreover, we found that HS treatment dose-dependently increased the activities of endogenous antioxidant enzymes (SOD and CAT) as well as decreased the levels of oxidative products (8-iso-PGF2α and MDA) and inflammatory cytokines (TNF-α and HMGB1) in injured ipsilateral brain tissues at 6 h, 12 h and 24 h after pMCAO operation (P<0.05). Thus, hydrogen-rich saline dose-dependently exerts a neuroprotective effect against permanent focal cerebral ischemia, and its beneficial effect is at least partially mediated by reducing oxidative stress and inflammation. Molecular hydrogen may be an effective therapeutic strategy for stroke patients.
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