氢气在缺血再灌注损伤性疾病及器官移植中的研究进展

黄俊隆 刘文武 孙学军*

doi:10.16098/j.issn.0529-1356.2018.03.023

PDF(290 KB)

解剖学报 ›› 2018, Vol. 49 ›› Issue (3) : 406-411. DOI: 10.16098/j.issn.0529-1356.2018.03.023

综述

氢气在缺血再灌注损伤性疾病及器官移植中的研究进展

黄俊隆¹ 刘文武² 孙学军^1*

作者信息 +

Advances in the effects and mechanisms of hydrogen on ischemia-reperfusion injury in diseases and organ transplantation

HUANG Jun-long¹ LIU Wen-wu² SUN Xue-jun^1*

Author information +

文章历史 +

摘要

在多种疾病的发生发展及器官移植的过程中，缺血再灌注损伤（I/R）是重要的病理生理学基础。氢气作为一种新的抗氧化剂，在多种器官缺血再灌注疾病和器官移植模型中的作用被广泛研究。这里，我们回顾与氢气治疗相关的缺血再灌注损伤性疾病及器官移植的研究进展，讨论氢气在器官缺血再灌注损伤中的保护效应和作用机制，并对未来研究进行展望。大量实验证据表明，氢气能够通过选择性抗氧化减少氧化应激，对抗炎症，减少凋亡，在不同的缺血再灌注疾病模型及器官移植中发挥显著的保护治疗作用。氢气对缺血再灌注损伤的作用研究为未来氢气医学临床应用奠定了基础，但相关机制和临床研究仍然需要进一步加强。

Abstract

Ischemiareperfusion (I/R) injury is a crucial pathophysiologic process in the development of various diseases or during organ transplantation. Hydrogen has been widely researched as a potential antioxidant in ischemia-reperfusion models of multiple diseases and organ transplantation. Herein, the authors review the current literature regarding the effects of hydrogen on ischemia-reperfusion injury and organ transplantation. Existing data on the effects and mechanisms of hydrogen on ischemia-reperfusion injury and organ transplantation are specifically reviewed and coupled with further suggestions for future work. In general, a substantial body of experimental evidence suggests that hydrogen significantly has a therapeutic effect on ischemia-reperfusion injury in models of multiple diseases and organ transplantation by inhibiting inflammatory response, oxidative stress and apoptosis through several underlying mechanisms. On this basis, further animal experiments and preliminary human clinical trial regarding the effects of hydrogen on ischemiareperfusion injury are need to be conducted for the early use of hydrogen as a drug in the clinic.

导出引用

黄俊隆刘文武孙学军. 氢气在缺血再灌注损伤性疾病及器官移植中的研究进展[J]. 解剖学报. 2018, 49(3): 406-411 https://doi.org/10.16098/j.issn.0529-1356.2018.03.023

HUANG Jun-long LIU Wen-wu SUN Xue-jun. Advances in the effects and mechanisms of hydrogen on ischemia-reperfusion injury in diseases and organ transplantation[J]. Acta Anatomica Sinica. 2018, 49(3): 406-411 https://doi.org/10.16098/j.issn.0529-1356.2018.03.023

参考文献

［1］Yellon DM, Hausenloy DJ. Myocardial reperfusion injury［J］. N Engl J Med, 2007, 357（11）: 1121-1135.

［2］Buravkova LB, D’Iachenko AI, Pavlov BN. The use of hydrogen as a component in breathing gas mixtures in deep-sea dives［J］. Usp Fiziol Nauk, 1992, 23（4）: 71-88.

［3］Dole M, Wilson FR, Fife WP. Hyperbaric hydrogen therapy: a possible treatment for cancer［J］. Science, 1975, 190（4210）: 152-154.

［4］Gharib B, Hanna S, Abdallahi OM, et al. Anti-inflammatory properties of molecular hydrogen: investigation on parasite-induced liver inflammation［J］. C R Acad Sci Ⅲ, 2001, 324（8）: 719-724.

［5］Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals［J］. Nat Med, 2007, 13（6）: 688-694.

［6］Liu CL, Zhang K, Chen G. Hydrogen therapy: from mechanism to cerebral diseases［J］. Med Gas Res, 2016, 6（1）: 48-54.

［7］Ichihara M, Sobue S, Ito M, et al. Beneficial biological effects and the underlying mechanisms of molecular hydrogen-comprehensive review of 321 original articles［J］. Med Gas Res, 2015, 5: 12.

［8］Oharazawa H, Igarashi T, Yokota T, et al. Protection of the retina by rapid diffusion of hydrogen: administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury［J］. Invest Ophthalmol Vis Sci, 2010, 51(1): 487-492.

［9］Zhai X, Chen X, Shi J, et al. Lactulose ameliorates cerebral ischemia-reperfusion injury in rats by inducing hydrogen by activating Nrf2 expression［J］. Free Radic Biol Med, 2013, 65: 731-741.

［10］Sobue S, Yamai K, Ito M, et al. Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents［J］. Mol Cell Biochem, 2015, 403(1-1): 231-241.

［11］Ohsawa I, Nishimaki K, Yamagata K, et al. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice［J］. Biochem Biophys Res Commun, 2008, 377(4): 1195-1198.

［12］Liu Y, Liu W, Sun X, et al. Hydrogen saline offers neuroprotection by reducing oxidative stress in a focal cerebral ischemia-reperfusion rat model［J］. Med Gas Res, 2011, 1(1): 15.

［13］Chen O, Cao Z, Li H, et al. High-concentration hydrogen protects mouse heart against ischemia/reperfusion injury through activation of thePI3K/Akt1 pathway［J］. Sci Rep, 2017, 7(1): 14871.

［14］Yue L, Li H, Zhao Y, et al. Effects of hydrogen-rich saline on Akt/GSK3beta signaling pathways and cardiac function during myocardial ischemia-reperfusion in rats［J］. Zhonghua Yi Xue Za Zhi, 2015, 95(19): 1483-1487.

［15］Sun Q, Kang Z, Cai J, et al. Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats［J］. Exp Biol Med (Maywood), 2009, 234(10): 1212-1219.

［16］Zhang Y, Sun Q, He B, et al. Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion［J］. Int J Cardiol, 2011, 148(1): 91-95.

［17］Nakao A, Kaczorowski DJ, Wang Y, et al. Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both［J］. J Heart Lung Transplant, 2010, 29(5): 544-553.

［18］Noda K, Shigemura N, Tanaka Y, et al. A novel method of preserving cardiac grafts using a hydrogen-rich water bath［J］. J Heart Lung Transplant, 2013, 32(2): 241-250.

［19］Noda K, Tanaka Y, Shigemura N, et al. Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration［J］. Transpl Int, 2012, 25(12): 1213-1222.

［20］Iketani M, Ohsawa I. Molecular hydrogen as a neuroprotective agent［J］. Curr Neuropharmacol, 2017, 15(2): 324-331.

［21］Cui J, Chen X, Zhai X, et al. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats-A possible new hydrogen resource for clinical use［J］. Neuroscience, 2016, 335: 232-241.

［22］Cui Y, Zhang H, Ji M, et al. Hydrogen-rich saline attenuates neuronal ischemia- -reperfusion injury by protecting mitochondrial function in rats［J］. J Surg Res, 2014, 192(2): 564-572.

［23］Li Q, Yu P, Zeng Q, et al. Neuroprotective effect of hydrogen-rich saline in global cerebral ischemia/reperfusion rats: up-regulated Tregs and down-regulated miR-21, miR-210 and NF-kappaB expression［J］. Neurochem Res, 2016, 41(10): 2655-2665.

［24］Zhou L, Wang X, Xue W, et al. Beneficial effects of hydrogen-rich saline against spinal cord ischemia-reperfusion injury in rabbits［J］. Brain Res, 2013, 1517: 150-160.

［25］Huang Y, Xie K, Li J, et al. Beneficial effects of hydrogen gas against spinal cord ischemia-reperfusion injury in rabbits［J］. Brain Res, 2011, 1378: 125-136.

［26］Takahashi M, Chen-Yoshikawa TF, Saito M, et al. Immersing lungs in hydrogen-rich saline attenuates lung ischaemia-reperfusion injury［J］. Eur J Cardiothorac Surg, 2017, 51(3): 442-448.

［27］Shi J, Yao F, Zhong C, et al. Hydrogen saline is protective for acute lung ischaemia/reperfusion injuries in rats［J］. Heart Lung Circ, 2012, 21(9): 556-563.

［28］Li H, Zhou R, Liu J, et al. Hydrogen-rich saline attenuates lung ischemia-reperfusion injury in rabbits［J］. J Surg Res, 2012, 174(1): e11-16.

［29］Kawamura T, Huang CS, Tochigi N, et al. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats［J］. Transplantation, 2010, 90(12): 1344-1351.

［30］Liu R, Fang X, Meng C, et al. Lung inflation with hydrogen during the cold ischemia phase decreases lung graft injury in rats［J］. Exp Biol Med (Maywood), 2015, 240(9): 1214-1222.

［31］Noda K, Shigemura N, Tanaka Y, et al. Hydrogen preconditioning during ex vivo lung perfusion improves the quality of lung grafts in rats［J］. Transplantation, 2014, 98(5): 499-506.

［32］Zhou H, Fu Z, Wei Y, et al. Hydrogen inhalation decreases lung graft injury in brain-dead donor rats［J］. J Heart Lung Transplant, 2013, 32(2): 251-258.

［33］Haam S, Lee S, Paik HC, et al. The effects of hydrogen gas inhalation during ex vivo lung perfusion on donor lungs obtained after cardiac death［J］. Eur J Cardiothorac Surg, 2015, 48(4): 542-547.

［34］Li H, Bai G, Ge Y, et al. Hydrogen-rich saline protects against small-scale liver ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress［J］. Life Sci, 2018,194:7-14.

［35］Li H, Chen O, Ye Z, et al. Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2A receptor mediated PI3K-Akt pathway［J］. Biochem Pharmacol, 2017, 130: 83-92.

［36］Zhang CB, Tang YC, Xu XJ, et al. Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by activating the NF-kappaB signaling pathway［J］. Exp Ther Med, 2015, 9（6）: 2114-2120.

［37］Liu Y, Yang L, Tao K, et al. Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release［J］. BMC Gastroenterol, 2014, 14: 12.

［38］Matsuno N, Watanabe R, Kimura M, et al. Beneficial effects of hydrogen gas on porcine liver reperfusion injury with use of total vascular exclusion and active venous bypass［J］. Transplant Proc, 2014, 46（4）: 1104-1106.

［39］Du H, Sheng M, Wu L, et al. Hydrogen-rich saline attenuates acute kidney injury after liver transplantation via activating p53-mediated autophagy［J］. Transplantation, 2016, 100（3）: 563-570.

［40］Chen H, Sun YP, Hu PF, et al. The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in rats［J］. J Surg Res, 2011, 167（2）: 316-322.

［41］Buchholz BM, Kaczorowski DJ, Sugimoto R, et al. Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury［J］. Am J Transplant, 2008, 8（10）: 2015-2024.

［42］Shigeta T, Sakamoto S, Li XK, et al. Luminal injection of hydrogen-rich solution attenuates intestinal ischemia-reperfusion injury in rats［J］. Transplantation, 2015, 99（3）: 500-507.

［43］Buchholz BM, Masutani K, Kawamura T, et al. Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation［J］. Transplantation, 2011, 92（9）: 985-992.

［44］Wang F, Yu G, Liu SY, et al. Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats［J］. J Surg Res, 2011, 167（2）: e339-344.

［45］Zeng K, Huang H, Jiang XQ, et al. Protective effects of hydrogen on renal ischemia/reperfusion injury in rats［J］. Journal of Sichuan University(Medical Science Edition), 2014, 45（1）: 39-42. (in Chinese)

曾葵，黄瀚，江晓琴，等. 氢气对大鼠肾脏缺血再灌注损伤的保护作用［J］. 四川大学学报（医学版），2014，45（1）：39-42.

［46］Li J, Hong Z, Liu H, et al. Hydrogen-rich saline promotes the recovery of renal function after ischemia/reperfusion injury in rats via anti-apoptosis and antiinflammation［J］. Front Pharmacol, 2016, 7: 106.

［47］Abe T, Li XK, Yazawa K, et al. Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury［J］. Transplantation, 2012, 94（1）: 14-21.

［48］Shingu C, Koga H, Hagiwara S, et al. Hydrogen-rich saline solution attenuates renal ischemia-reperfusion injury［J］. J Anesth, 2010, 24（4）: 569-574.

［49］Cardinal JS, Zhan J, Wang Y, et al. Oral hydrogen water prevents chronic allograft nephropathy in rats［J］. Kidney Int, 2010, 77（2）: 101-109.

［50］Liu G, Song D, Jiang Y, et al. Effect of hydrogen-saline on lung injury and heme oxygenase-1 expression in the lung tissue of acute paraquat-intoxicated mice［J］. Chinese Journal of Industrial Hygiene and Occupational Diseases, 2015, 33(5): 337-341. (in Chinese)

刘刚，宋冬梅，江宇，等. 氢盐水对百草枯中毒小鼠急性肺损伤及肺组织血红素氧化酶-1表达的影响［J］. 中华劳动卫生职业病杂志，2015，33（5）：337-341.