孙学军
氢气治疗脊髓损伤的机制研究
2014-6-17 11:30
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第二军医大学长征医院麻醉科学袁红斌教授课题组,前期研究证明,氢气对脊髓损伤的具有治疗作用,但对其治疗作用机制并不十分了解。最近袁红斌教授课题组进一步研究证明,氢气所以能治疗脊髓损伤,主要是通过抑制氧化损伤相关星形胶质细胞增生,并对和星形胶质细胞增生关系密切的细胞信号分子STAT3磷酸化、活性氧和相关炎症因子的变化进行的分析。该研究目前已经发表在CNS Neurosci Ther. 2014 doi: 10.1111/cns.12258。

脊髓损伤是导致人类瘫痪的重要原因,给患者和家庭带来极大痛苦和经济负担。随着世界各国经济水平的发展,脊髓损伤发生率呈现逐年增高的趋势。在发达国家,脊髓损伤的发生率大约为13.3-45.9人/百万人/年,我国上海市1991年统计的脊髓创伤发生率为34.3人/百万人,北京市2002年脊髓创伤发病率为60人/百万人。脊髓损伤是脊柱创伤最严重的并发症,往往导致损伤节段以下肢体严重的功能障碍。脊髓损伤不仅会给患者本人带来身体和心理的严重伤害,还会对整个社会造成巨大的经济负担。在美国,由于脊髓损伤所导致的社会经济损失大约为80亿美元/年。针对脊髓损伤的预防、治疗和康复已成为当今医学界的一大课题。

值得注意的是,从目前所开展的研究看,氢气所以对脊髓损伤具有治疗作用,只是针对脊髓损伤后引起的局部组织氧化损伤、炎症反应和细胞增生产生的影响。中枢神经损伤后局部炎症是导致疾病加重的重要因素,对抗炎症和氧化损伤能产生一定效果是值得肯定的,当然动物实验结果不能直接证明人体有效,因此这方面仍需要开展临床研究确认。另外,从目前所了解治疗机制角度,氢气对脊髓损伤并不能解决神经再生的问题,因此对陈旧性脊髓损伤不可能产生效果。不过,脊髓损伤瘫痪的患者,可能存在消化道紊乱,缺乏运动带来的代谢性疾病问题,使用氢气治疗或许能产生理想效果。总之,氢气绝对不是万能药,不可能包治百病,但考虑到氢气的巨大安全性,以及其治疗基础是对抗氧化和炎症,对多种疾病都有可能产生一定效果,因此许多疾病都值得尝试。

袁红斌教授是国际上最早开展氢气生物学研究的学者之一,早在2009年他就率先在国际上发表氢气治疗小肠缺血再灌注损伤,在国际上最早开展氢气对抗疼痛效应的研究,氢气对脊髓创伤损伤保护研究。目前共发表相关论文4篇。

CNS Neurosci Ther. 2014 doi: 10.1111/cns.12258.

Molecular Hydrogen Suppresses Reactive Astrogliosis Related to Oxidative Injury during Spinal Cord Injury in Rats.

Liu FT1, Xu SM, Xiang ZH, Li XN, Li J, Yuan HB, Sun XJ.

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·          1Department of Anesthesiology, Neuroscience Research Centre, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Spinal cord injury (SCI) can induce excessive astrocyte activation. Hydrogen has been deemed as a novel antioxidant. We investigated whether molecular hydrogen could act as an antiastrogliosis agent during SCI and oxidative injury in experimental rats and cultured astrocytes.

Hydrogen-rich saline (HS, 8 mL/kg, i.p.) was injected every 12 h after SCI in rats. The expression of STAT3, p-STAT3, and glial fibrillary acidic protein (GFAP); the release of IL-1β, IL-6, and TNF-α; and astrogliosis, along with the BBB score, were evaluated. Culturing astrocytes with hydrogen-rich medium, the intracellular reactive oxygen species (ROS), astrogliosis, and the release of proinflammatory cytokines were assessed after H2 O2 -induced injury.

In the HS group, the expression of STAT3, p-STAT3, and GFAP and the proinflammatory cytokines were decreased in local spinal cord on postoperation day (POD) 3; on PODs 7 and 14, reactive astrogliosis was suppressed, and the locomotor function was also improved. Furthermore, hydrogen-rich medium attenuated the intracellular production of ROS (especially HO•), astrogliosis, and the secretion of proinflammatory cytokines in astrocytes 12 h after H2 O2 -induced injury.

Molecular hydrogen could suppress reactive astrogliosis after contusive SCI and reduce the release of proinflammatory cytokines produced by active astrocytes related to oxidative injury. Thus, molecular hydrogen is potential to be a neuroprotective agent.

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