来自长海医院胸外科的研究发现，只要把氢气溶解到器官保存液（HTK）中，心脏保存的效果明显提高。该研究论文最近发表在《国际心脏学》杂志上，这是氢气在器官移植领域的一个重要进展，由于几年前美国学者证明呼吸氢气对器官移植后损伤具有保护作用，本研究证明体外用氢气同样可以增加心脏保存效果，这样就可以把氢气从器官保存到移植后损伤进行全程使用，应该可以达到更理想的效果（尚无直接证据）。体外应用氢气，相对在体使用，更容易获得临床使用的批准，这将加快氢气进入临床应用的步伐。

本研究采用多种方法，证明氢气溶解到保存液中可以降低器官保存过程由于冷缺血导致的心脏细胞凋亡蛋白基因表达，降低凋亡蛋白水平，增加抗氧化能力，降低氧化损伤和炎症因子的释放。关于炎症因子的改变，相对的贡献应该比较小，因为体外器官缺乏必要的炎症细胞来源，如果结合在体研究，将可以把本研究提高一个层次。非常令人激动的一个细节：把动物心脏放在4度保存数小时后，无氢气的心脏恢复37度后恢复跳动的时间大概是4分钟，而保护液中含氢气的心脏恢复时间降低到1分钟。这个表观效果虽然没有采用高端的实验技术，但绝对说明问题。因此，有时候实验细节和相对粗糙的方法更能说明问题。

当然，本研究仍属于描述性研究，亮点是首次证明器官保存效果和相关影响因素。但氢气是如何引起这些改变的分子途径并无法获得确认。例如引起凋亡蛋白基因表达的上游调节分子非常复杂，那些通路是最关键的，至少需要那些路径参与这个保护效应，都值得深入探讨。特别需要进行阻断性影响观察是否可以翻转氢气的保护效应，来确认这些通路的重要性。当然这些工作存在一定难度和风险。到目前长海医院成为国内唯一一个发表氢气生物学效应在5分以上杂志的单位，值得高兴，也是国内发表氢气生物学效应论文最多（8篇）的医院，分别是麻醉科、急救科、眼科、耳鼻、烧伤和胸外科。

Int J Cardiol. 2012 Jan 19. [Epub ahead of print]

Hydrogen as additive of HTK solution fortifies myocardial preservation in grafts with prolonged cold ischemia.

Tan M, Sun X, Guo L, Su C, Sun X, Xu Z.

Source

Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.

Abstract

BACKGROUND:

Recent evidences indicated that hydrogen (H(2)) can attenuate organ transplantation induced cold ischemia/reperfusion (I/R) injury if administrated perioperatively. In this study we evaluated whether administrating H(2) during the prolonged cold ischemia stage by adding it to Histidine-Tryptophan-Ketoglutarate (HTK) solution fortifies preservation for cardiac grafts.

METHODS:

One hundred and twenty-eight Sprague-Dawley (SD) rats were equally randomized to four groups: three H(2)-rich HTK-treated groups with H(2) of different concentrations and traditional HTK-treated group as the control group. Isolated hearts were mounted on the Langendorff apparatus for aerobic perfusion. Following baseline hemodynamic measurements, grafts were arrested and stored in HTK with or without H(2) for 6h at 4°C. After this prolonged cold storage, grafts were reperfused and concerned parameters were examined.

RESULTS:

Compared with the control group, preservation in H(2)-rich HTK significantly enhanced the percentage recovery of hemodynamic parameters, which was parallel to the diminished re-beating time and improved microscopic morphology of myocardium. Oxidative stress associated parameters including 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were decreased while myocardial superoxide dismutase (SOD) activity was preserved. Concentrations of inflammatory mediators including tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6), percentage of TUNEL-positive cells, expression of pro-apoptotic molecule Bax, and caspase-3 activity were reduced while Bcl-2 mRNA and protein levels were up-regulated in H(2)-rich HTK groups. The protective effects of H(2) were concentration dependant.

CONCLUSIONS:

Hydrogen as additive of HTK solution fortifies HTK's preservation efficacy for cardiac grafts subjected to prolonged cold ischemia by inhibiting cold ischemia-induced up-regulation of oxidative stress, inflammation mediators, and apoptosis.
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