氢气可以作为体外器官保护剂

Nakao小组再发表氢气医学领域的重要文献。早在2008年，Nakao小组证明呼吸氢气对小肠移植后炎症反应具有治疗作用，首先提出氢气具有抗炎症的作用。后来他们在心脏、肾脏等器官移植方面发表同类的研究文章。在器官移植领域，存在一个非常重要的问题，就是器官体外保存时间的问题。例如人的肝脏从贡体取出后放在器官保护液中，可以持续12小时左右再移植给受体，可以没有问题。但随着体外保存的时间延长，器官移植后的存活率会显著下降。主要的问题是器官保存的过程中是一个器官缺血缺氧的过程，尽管采取一些措施，例如给一定的细胞保护剂，低温等。但仍不能明显延长保存时间。体外器官保护是器官移植领域的一个重要问题。因为这大大限制了不同地区之间的器官转运，例如现在基本无法实现10个小时以上运输的器官移植的需要，中国的器官供应者不能运到欧洲和美国。同样美国和欧洲的也不能送到中国使用。因此寻找更有效的保护方法是这个领域一直关注的重要问题。

08年的时候我先后与一些作器官移植的老师探讨过这个问题，也进行了一些尝试，但当时我们的试验并不成功，后来就没有继续。现在美国的Nakao教授把这个问题解决了。他们采用小肠移植模型，证明了使用氢气可以有效保护体外器官保护的时间，并能显著降低移植后的器官损伤。并证明这种保护与抗氧化酶HO-1和抗炎症作用的增强有关系。主要可能是他们采用的研究手段比较巧妙，一是采用连续通气的方法，另一个是对照采用连续氮气，这可能避免了氧分压的影响。因为无论氢气通风，还是氮气，液体中氧气浓度肯定会降低到几乎没有，没有氧气是好事，还是不好，不得而知，但肯定非常重要。

相信用类似的研究模式开展心脏、肝脏、肾脏、皮肤、肺等器官移植的工作随后将大量出现，谁的动作快，谁的设计巧妙，谁就可以发表更好的文章。

Transplantation. 2011 Sep 27. [Epub ahead of print]

Hydrogen-Enriched Preservation Protects the Isogeneic Intestinal Graft and Amends Recipient Gastric Function During Transplantation.

Buchholz BM, Masutani K, Kawamura T, Peng X, Toyoda Y, Billiar TR, Bauer AJ, Nakao A.

Source

1 Department of Medicine, University of Pittsburgh, Pittsburgh, PA. 2 Department of Surgery, University of Bonn, Bonn, Germany. 3 Department of Pathology, University of Pittsburgh, Pittsburgh, PA. 4 Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA. 5 Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA. 6 Department of Surgery, University of Pittsburgh, Pittsburgh, PA.

Abstract

BACKGROUND.: Inhaled hydrogen gas exerts antioxidant and anti-inflammatory effects in rat intestinal transplantation. Here, we investigated whether ex vivo donor organ treatment with dissolved hydrogen would prevent intestinal graft injury. METHODS.: Isogeneic intestinal transplantation was performed in Lewis rats with vascular flush, luminal preservation, and cold graft storage in nitrogen-bubbled (SITxN2) or hydrogen-bubbled (SITxH2) preservation solution. Lactated Ringer's solution and 3-hr cold ischemia time were used for mechanistic investigations, whereas survival experiments were performed with University of Wisconsin solution and 6-hr cold ischemia time. RESULTS.: During the early phase of ischemia-reperfusion injury, hydrogen-enriched solution significantly preserved mucosal graft morphology, diminished graft malondialdehyde levels demonstrating substantial reduction potential and blunted proinflammatory molecular responses (early growth response gene [EGR-1], interleukin [IL]-6, IL-1ß, and inducible nitric oxide synthase) within the reperfused intestinal graft muscularis. During the late phase of ischemia-reperfusion injury, circulating IL-6 protein and lactate dehydrogenase levels were significantly ameliorated in SITxH2 animals, which were associated with a favorable functional outcome in in vivo liquid gastrointestinal transit and recipient solid gastric emptying of chrome steel balls, and marked prevention of the posttransplant associated suppression of in vitro muscarinic jejunal contractility. Reflecting improved graft preservation, hydrogen preloading of grafts increased recipient survival rates from 41% to 80%. Anti-inflammatory and antiapoptotic heme oxygenase-1 was significantly upregulated in the hydrogen-treated graft muscularis but not mucosa before reperfusion. CONCLUSIONS.: Graft preloading with hydrogen demonstrated superior morphologic and functional graft protection in rodent intestinal transplantation, ultimately facilitating recipient survival. Antioxidant capacity and muscularis heme oxygenase-1 upregulation are possible protective mechanisms