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氢气对新生儿窒息性神经血管病变的保护作用
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自从2007年有学者发现氢气的生物学效应以来，国际大量学者先后证明氢气对几十种重要疾病和损伤，如脑缺血、神经退行性疾病、各类炎症和创伤等具有明显的治疗作用。关于氢气治疗疾病的机制，目前学术领域普遍认为主要是通过选择性中和毒性自由基，减少组织氧化损伤、炎症反应和细胞凋亡，产生对各类疾病引起的组织伤害，发挥治疗作用。临床研究也证明对类风湿关节炎、巴金森病、糖尿病、代谢综合征、肿瘤放射治疗副作用、血液和腹腔透析副作用等具有治疗价值。氢气生物学研究目前已经成为国际生物医学研究的热点，但其中90%以上的研究来自中国、日本和美国学者。来自欧洲和其他国家地区的学者比较少，不过最近一年来自欧洲等地区的研究逐渐增加，显示了该研究领域的巨大发展潜力。这里介绍刚刚发表的来自欧洲匈牙利一个研究。
匈牙利塞格德大学生理系Oláh O等最近在新生儿学Neonatology杂志发表一篇论文，证明氢气对新生猪窒息引起的神经血管功能异常具有保护作用。
新生儿窒息(asphyxia of newborn)，为胎儿娩出后一分钟，仅有心跳而无呼吸或未建立规律呼吸的缺氧状态。为新生儿死亡的主要原因之一，是出生后最常见的紧急情况，必须积极抢救和正确处理，以降低新生儿死亡率及预防远期后遗症。
过去曾有多篇研究论文探讨氢气对新生儿窒息引起的脑组织和功能损伤的保护作用。不过需要特别强调的是，这些研究采用的干预措施都是在窒息发生后的早期，并不是针对新生儿窒息引起远期后遗症。也就是说，有不少出生发生窒息导致的儿童和成年患者的疾病，例如癫痫、脑功能异常，并不是这些研究针对的问题。或者说对这种疾病只是在早期损伤阶段的对抗，因为许多人会根据这些研究联想到对后遗症的治疗作用。
氢气通过选择性抗氧化发挥神经保护作用，新生儿窒息可以导致脑血管功能异常，这种异常和窒息导致的氧化损伤关系密切。氢气是否可以通过对抗氧化损伤缓解窒息引起的脑血管功能异常过去未见报道。本研究针对这一问题，采用猪新生儿窒息模型（窒息8分钟），研究呼吸2.1%氢气4小时对窒息引起的脑血管功能异常的作用。通过检测N甲基D门冬氨酸、二氧化碳、去甲肾上腺素和硝普钠引起的大脑软膜动脉血管反应，研究血管调节功能；采用组织形态学研究组织病理学变化。结果发现，窒息后24小时血流动力学、血气和核心体温没有发生改变，对去甲肾上腺素和硝普钠引起血管反应没有明显影响，但可以明显影响N甲基D门冬氨酸、二氧化碳引起的脑血管反应（核心问题）。和呼吸空气组相比，呼吸氢气组动物N甲基D门冬氨酸、二氧化碳引起的脑血管反应异常显著好转，同时脑组织病理学改变明显缓解。研究结果提示，氢气对新生儿窒息引起的脑血管调节功能异常具有潜在的治疗价值。这是国际上首次采用脑血管功能分析证明氢气的生物学作用，也是目前来自欧洲学者为数不多关于氢气生物学效应的研究论文。
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Delayed Neurovascular Dysfunction Is Alleviated by Hydrogen in Asphyxiated Newborn Pigs Oláh O.a · Tóth-Szűki V.a · Temesvári P.c · Bari F.b · Domoki F.a Departments ofaPhysiology andbMedical Physics and Informatics, Faculty of Medicine, University of Szeged, Szeged, andcDepartment of Pediatrics, University Teaching Hospital Orosháza, Orosháza, Hungary |
Abstract
Background: The neurovascular unit encompasses the functional interactions of cerebrovascular and brain parenchymal cells necessary for the metabolic homeostasis of neurons. Previous studies indicated marked but only transient (1-4 h) reactive oxygen species-dependent neurovascular dysfunction in newborn pigs after severe hypoxic/ischemic (H/I) stress contributing to the neuronal injury after birth asphyxia. Objectives: Our major purpose was to determine if neurovascular dysfunction would also occur later, at 24 h after a milder H/I stress. We also tested if the putative hydroxyl radical scavenger hydrogen (H2) exerted neurovascular protection. Methods: Anesthetized, ventilated piglets were assigned to three groups of 9 animals: time control, asphyxia/reventilation with air, and asphyxia/reventilation with air +2.1% H2 for 4 h. Asphyxia was induced by suspending ventilation for 8 min. Cerebrovascular reactivity (CR) of pial arterioles was determined using closed cranial window/intravital microscopy 24 h after asphyxia to the endothelium-dependent cerebrovascular stimulus hypercapnia, the neuronal function-dependent stimulus N-methyl-D-aspartate (NMDA), norepinephrine, and sodium nitroprusside. The brains were subjected to histopathology. Results: Hemodynamic parameters, blood gases, and core temperature did not differ significantly among the experimental groups. In the early reventilation period, the recovery of electroencephalographic activity was significantly better in H2-treated animals. Asphyxia/reventilation severely attenuated CR to hypercapnia and NMDA; however, reactivity to norepinephrine and sodium nitroprusside were unaltered. H2 fully or partially preserved CR to hypercapnia or NMDA, respectively. Histopathology revealed modest neuroprotection afforded by H2. Conclusions: Severe stimulus-selective delayed neurovascular dysfunction develops and persists even after mild H/I stress. H2 alleviates this delayed neurovascular dysfunction that can contribute to its neuroprotective effect.
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