The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits .pdf

氢气治疗疾病的研究论文非常多，最近日本学者报道呼吸氢对心搏骤停后脑损伤的保护作用，并和低温治疗进行比较，发表呼吸氢的效果甚至比国际公认的低温治疗相似。最近来自中山医科大学附属第一医院急诊科黄国庆等发表在Resuscitation的论文“neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest”也属于心搏骤停后脑损伤用氢保护的研究。但该研究提出了一种新的使用氢气的手段，就是通过注射氢的手段。前几日来自德国的学者曾经有关于氢气皮下注射后气体吸收规律的研究，就是发现氢气可以迅速被周围组织吸收，同时组织内的其他气体成分会扩散到气泡的现象。黄国庆等的论文是采用腹腔注射氢的方法治疗疾病，在临床上也同样存在组织内或身体内注射气体的情况，例如气脑脊液造影时就是向颅内注入气体(如空气、氧气等)，所得的脑室系统X图像为阴性(透光)图像。而腹腔镜则会向腹腔内大量注射气体以达到暴露手术操作区的目的。眼科也有用气体的压力治疗视网膜脱离的治疗手段。这说明身体内注射气体确实是可行的。而由于氢的溶解度非常低，通过注射的方式可以给局部组织提供非常高的氢气浓度，这当然对利用氢气没有问题，但也可能存在一种可能，就是局部组织氧气的浓度相对降低，导致局部组织缺氧的可能。其实，注射气体例如注射氧气、甲烷、氦气和氢气都可以作为治疗手段，至少都可以进行研究，一方面确定注射气体的可能效应，研究这些气体的效应机制，另一方面也必须考虑注射气体可能带来的不利影响。

黄国庆，詹蔚，文明祥，胡春林，李颖庆，李欣，魏红艳，廖晓星

（中山大学附属第一医院急诊科，广州 510080）

心搏骤停（cardical arrest, CA）是严重威胁人们生命安全的一种急症，其最大特点是突发性，预后差。自20世纪60年代推广“标准化”的心肺复苏(cardiopulmonary resuscitation，CPR)技术及近年随“生存链（chain of survival）”等复苏理念在院前急救的广泛应用，至2009年公布的多中心调查[1]显示院外CA患者复苏后自主循环恢复（restoration of spontaneous circulation，ROSC）率在室颤患者达49.7%，在电机械分离患者达35.1%，室颤患者院外复苏后一月存活率可达30%以上，但其中约50％的病人伴有中到重度的神经功能障碍。故如何进一步提高复苏成功率尤其是脑复苏成功率仍是急诊医学领域的研究重点。心搏骤停后全身缺血再灌注损伤是最重要的病理生理过程，氧化应激和炎症是缺血再灌注损伤产生的最重要因素[2]。脑缺血再灌注损伤后，神经胶质细胞、炎症细胞、内皮细胞激活并释放大量活性氧和炎症因子，炎症反应与氧化应激相互促进，共同造成组织损伤。2007年日本学者发现吸入2%氢气可成功减少脑卒中大鼠模型脑死面积并改善预后，氢气被认为具有选择性抗氧化应激作用[3]。此后众多学者用不同的动物模型验证了氢气对各组织器官缺血再灌注损伤的保护作用[4-6]。本研究拟用兔心搏骤停模型探讨是否氢气在全身缺血再灌注损伤情况下亦可发挥器官保护尤其是脑保护作用。

The neuroprotective effects of intraperitoneal injection of hydrogen in rabbits with cardiac arrest

·         Guoqing Huang^{a, b, 1},

·         ^a Department of Emergency, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China

·         ^b Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, China

·         ^c Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China

Received 9 July 2012

Revised 11 October 2012

Accepted 18 October 2012

Available online 27 October 2012

·         http://dx.doi.org/10.1016/j.resuscitation.2012.10.018, How to Cite or Link Using DOI

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Abstract

Objective

The purpose of this study was to investigate the neuroprotective effects of intraperitoneal injection of hydrogen (H₂) in rabbits with cardiac arrest (CA).

Methods

A rabbit model of CA was established by the delivery of alternating current between the esophagus and chest wall to induce ventricular fibrillation. Before CA, the animals were randomly divided into four groups: a sham group (no CA), a CA group, a CA + low dose (10 ml/kg) H₂ group (CA + H₂ group 1), and a CA + high dose (20 ml/kg) H₂ group (CA + H₂ group 2). In the first experiment, animals were observed for 72 h after the restoration of spontaneous circulation (ROSC). The neurological scores were assessed at 24, 48 and 72 h after ROSC. The rabbits that survived until 72 h were sacrificed using an overdose of anesthetic, and the brain tissues were collected and Nissl-stained to observe nerve cell damage in the hippocampal CA1 area. In addition, TUNEL assay was performed to detect apoptosis. In the second experiment, animals were observed for 6 h after ROSC. Blood samples and brain hippocampal tissues were collected, and differences in oxidative stress indicators were compared among the four groups.

Results

Intraperitoneal injection of H₂ improved the 72-h survival rate and neurological scores, reduced neuronal injury and inhibited neuronal apoptosis. Intraperitoneal injection of H₂ reduced oxidative stress indicators in the plasma and hippocampal tissues and enhanced antioxidant enzyme activity. No significant difference was observed between the two CA groups treated with different doses of H₂.

Conclusions

Intraperitoneal injection of H₂ is a novel hydrogen administration method and can reduce cerebral ischemia-reperfusion injury and improve the prognosis of cardiopulmonary cerebral resuscitation in a rabbit model of CA.