日本儿童健康很发育中心Naoto Matsuno最近在TransplantationProceedings杂志发表了一篇论文Beneficial Effects of Hydrogen Gas onPorcine Liver Reperfusion Injury With Use of Total Vascular Exclusion andActive Venous Bypass。研究证明氢气在肝脏器官移植中的潜在应用前景。
肝脏缺血再灌注损伤是肝脏器官移植过程中的很容易发生的组织损伤类型，对移植肝脏的成活有很大影响。活性氧的大量产生是组织缺血再灌注损伤中的关键因素。最近大量研究证明，氢气具有选择性中和毒性自由基，保护氧化损伤的作用，对各类器官缺血再灌注损伤的治疗效果都十分理想。但过去的研究并没有采用大型动物研究肝脏组织再灌注损伤，最新这一研究是希望采用猪肝脏缺血再灌注损伤模型，验证氢气的保护效应，探讨这种气体在肝脏移植中保护缺血再灌注损伤的潜在治疗效果。
6只体重20公斤的远交猪用于实验，左股静脉很脾脏静脉吻合，并使用离心泵将脾静脉血液输入左颈内静脉，然后将肝脏所有血管钳夹，使肝脏血液循环（动脉静脉全部）完全停止60分钟，用5 ppm（4倍饱和浓度，这个很厉害），氢气饱和的乳酸林格氏液通过门静脉给肝脏灌注（实验组再灌注前灌注这种保护液，对照组的6只猪灌注无氢气的普通乳酸林格氏液）。
结果发现，对照组天冬氨酸转氨酶水平（肝功能指标）在恢复血流30、60和120分钟后分别达到1560.3、1925.3和 2342.5 IU/L，而经过氢气饱和水治疗组则是175.3、200.7和 661.0 IU/L。乳酸脱氢酶（细胞损伤指标）对照组分别为23235.0、3496.7和4793.5，而经过氢气饱和水治疗组则是663.3、802.0和983.7 IU/L。肝脏组织中氢气浓度再灌注时升高到954.6 ppm，但30分钟后完全消失。
本研究结果表明，氢气饱和的灌注液作为肝脏灌流液是安全的，并能显著保护猪肝脏缺血再灌注损伤导致的肝脏损伤，这种研究模式非常接近于人类器官移植的情况，提示在人类器官移植过程中作为器官保护液的潜在可行性。
NaotoMatsuno, MD, PhD, Department of Innovative and Transplant Surgery, NationalCenter for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo,157-8535, Japan.
Background
Liverischemia/reperfusion (I/R) injury is a high risk factor in livertransplantation and it influences graft survival. One of the major eventsduring I/R injury is the generation of cytotoxic oxygen radicals. Recently,hydrogen gas has been reported to have antioxidant properties and protectiveeffects against organ dysfunction induced by I/R injury. The aim of this studyis to investigate effects of hydrogen on porcine liver reperfusion injury.
Materialsand Methods
Sixoutbred pigs weighing 20 kg were used for the experiment. Under generalanesthesia, the venous bypass between the left femoral vein and the splenic veinto the left jugular vein was made using a centrifugal pump. Then, we used atotal vascular exclusion clamp (all in- and out-flow to the liver was clamped)for 60 minutes. Hydrogen (5 ppm) saturated with lactate Ringer's solution wasprepared. This solution was infused through the portal vein just beforereperfusion (hydrogen group).
Results
Aspartateaminotransferase levels in the control versus hydrogen group in 30, 60, and 120minutes after reperfusion were 1560.3, 1925.3, and 2342.5 versus 175.3, 200.7,and 661.00 IU/L, respectively. Lactate dehydrogenase (LDH) levels in thecontrol versus hydrogen groups in 30, 60, and 120 minutes after reperfusionwere 23,235.0, 3496.7, and 4793.5 versus 663.3, 802.0, and 983.7 IU/L,respectively. The hydrogen gas level in liver tissue increased to 954.6 ppmimmediately after reperfusion; however, it disappeared within 30 minutes.
Conclusion
Thesolution containing hydrogen gas was safe and had remarkably protective effectson the porcine during liver I/R and may be applied in the clinical setting.
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