氢分子在临床应用中的研究进展
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摘要
氢分子是一种具有弱还原性的双原子分子。近年来研究发现,氢分子具有广泛的生物学效应,氢分子的抗炎、抗氧化作用在大量动物疾病模型及临床试验中得到证实。目前已发现氢分子在超过200种疾病中均显示出一定的治疗效果,并在初步的临床试验中取得了相似的结果。主要对氢分子在肿瘤、代谢相关疾病、神经系统疾病以及其他氧化应激及炎症相关疾病中的临床应用进展进行了综述,以期为研究人员进行大规模、多中心临床研究以及对氢分子更深层次的作用机制研究提供参考。
Hydrogen molecule is a kind of diatomic molecule with weak reducibility. Recent studies have found that hydrogen molecules have a wide range of biological effects. The anti-inflammatory and antioxidant effects of hydrogen molecules have been confirmed in a large number of animal disease models and clinical trials. At present, it has been found that hydrogen molecules have shown certain therapeutic effects on more than 200 diseases, and similar results have been achieved in preliminary clinical trials. The progress on clinical application of hydrogen molecule in tumors, metabolic diseases, nervous system diseases and other oxidative stress and inflammatory related diseases were mainly reviewed, in order to provide a reference for researchers to carry out large-scale, multi-center clinical studies and to study the deeper action mechanism of hydrogen molecules.
Hydrogen molecule is a kind of diatomic molecule with weak reducibility. Recent studies have found that hydrogen molecules have a wide range of biological effects. The anti-inflammatory and antioxidant effects of hydrogen molecules have been confirmed in a large number of animal disease models and clinical trials. At present, it has been found that hydrogen molecules have shown certain therapeutic effects on more than 200 diseases, and similar results have been achieved in preliminary clinical trials. The progress on clinical application of hydrogen molecule in tumors, metabolic diseases, nervous system diseases and other oxidative stress and inflammatory related diseases were mainly reviewed, in order to provide a reference for researchers to carry out large-scale, multi-center clinical studies and to study the deeper action mechanism of hydrogen molecules.
引文
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[2] Sano M,Suzuki M,Homma K,et al..Promising novel therapy with hydrogen gas for emergency and critical care medicine[J].Acute Med.Surg.,2018,5(2):113-118.
[3] Ge L,Yang M,Yang N N,et al..Molecular hydrogen:A preventive and therapeutic medical gas for various diseases[J].Oncotarget,2017,8(60):102653-102673.
[4] Dohi K,Satoh K,Miyamoto K,et al..Molecular hydrogen in the treatment of acute and chronic neurological conditions:Mechanisms of protection and routes of administration[J].J.Clin.Biochem.Nutr.,2017,61(1):1-5.
[5] 赵岭.有机磷农药生物毒性及氢保护作用的研究[D].北京:北京工业大学,博士学位论文,2013.
[6] Zhang X,Liu J,Jin K,et al..Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes[J].J.Diabetes Invest.,2018,9(1):83-90.
[7] Shang L,Xie F,Li J,et al..Therapeutic potential of molecular hydrogen in ovarian cancer[J].Transl.Cancer Res.,2018,7(4):988-995.
[8] Shao A,Wu H,Hong Y,et al..Hydrogen-rich saline attenuated subarachnoid hemorrhage-induced early brain injury in rats by suppressing inflammatory response:Possible involvement of NF-κB pathway and NLRP3 inflammasome[J].Mol.Neurobiol.,2016,53(5):3462-3476.
[9] Bedini N,Cicchetti A,Palorini F,et al..Evaluation of mediators associated with the inflammatory response in prostate cancer patients undergoing radiotherapy[J].Dis.Markers,2018,25(2):1-9.
[10] Kang K M,Kang Y N,Choi I B,et al..Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors[J].Med.Gas Res.,2011,11(1):2-8.
[11] 许长春,李燕飞,刘承军,等.富氢水防治放射性口腔粘膜反应110例临床观察[J].中国辐射卫生,27(4):363-365.
[12] Grothey A,Sobrero A F,Shields A F,et al..Duration of adjuvant chemotherapy for stage III colon cancer[J].New Engl.J.Med.,2018,378(13):1177-1188.
[13] 杨庆玺.探讨富氢水在恶性肿瘤病人化疗中的减毒增效作用[D].山东泰安:泰山医学院,硕士学位论文,2014.
[14] 郑延松,韩超进,陈志来,等.氢气对男性高尿酸血症治疗效果的研究[J].中国临床保健杂志,2017,20(2):118-121.
[15] Dai W J,Ye L,Liu A Z,et al..Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus:A meta-analysis[J].Medicine,2017,96(39):e8179.
[16] Kajiyama S,Hasegawa G,Asano M,et al..Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance[J].Nutr.Res.,2008,28(3):137-143.
[17] 周晓,钱程,吕娇,等.氢气对社区糖尿病患者氧化应激的作用及影响因素[J].社区医学杂志,2018(12):1-3.
[18] Hjort R,Ahlqvist E,Carlsson P O,et al..Overweight,obesity and the risk of LADA:Results from a Swedish case-control study and the Norwegian HUNT Study[J].Diabetologia,2018,61(6):1333-1343.
[19] Korovljev D,Trivic T,Drid P,et al..Molecular hydrogen affects body composition,metabolic profiles,and mitochondrial function in middle-aged overweight women[J].Ir.J.Med.Sci.,2018,187(1):85-89.
[20] Nasreddine L,Tamim H,Itani L,et al..A minimally processed dietary pattern is associated with lower odds of metabolic syndrome among Lebanese adults[J].Public Health Nutr.,2018,21(1):160-171.
[21] 李敏.富氢水对社区代谢综合征患者血脂及高密度脂蛋白功能的影响[D].山东泰安:泰山医学院,硕士学位论文,2013.
[22] Nakao A,Toyoda Y,Sharma P,et al..Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome—An open label pilot study[J].J.Clin.Biochem.Nutr.,2010,46(2):140-149.
[23] Song G,Li M,Sang H,et al..Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome[J].J.Lipid Res.,2013,54(7):1884-1893.
[24] Jofre-Monseny L,Minihane A M,Rimbach G.Impact of apoE genotype on oxidative stress,inflammation and disease risk[J].Mol.Nutr.Food Res.,2008,52(1):131-145.
[25] Nishimaki K,Asada T,Ohsawa I,et al..Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment[J].Curr.Alzheimer Res.,2018,15(5):482-492.
[26] Hayashida K,Sano M,Kamimura N,et al..Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management[J].Circulation,2014,130(24):2173-2180.
[27] Ono H,Nishijima Y,Ohta S,et al..Hydrogen gas inhalation treatment in acute cerebral infarction:A randomized controlled clinical study on safety and neuroprotection[J].J.Stroke Cerebrovas.Dis.,2017,26(11):2587-2594.
[28] Chen X,Cui J,Zhai X,et al..Inhalation of hydrogen of different concentrations ameliorates spinal cord injury in mice by protecting spinal cord neurons from apoptosis,oxidative injury and mitochondrial structure damages[J].Cell.Physiol.Biochem.,2018,47(1):176-190.
[29] 张哲.高浓度氢气吸入治疗脊髓损伤的基础和临床研究[D].安徽蚌埠:蚌埠医学院,硕士学位论文,2017.
[30] 漆楠楠,杨琳,李希红,等.富氢水治疗新生儿缺氧缺血性脑病疗效分析[J].泰山医学院学报,2016,37(12):1331-1332.
[31] Liu X,Yu Y,Zhu S.Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD):A meta-analysis of observational studies[J].PLoS ONE,2018,13(4):e0195659.
[32] 王如意.氢气吸入对骨科老年患者术后认知功能障碍的影响[D].天津:天津医科大学,硕士学位论文,2017.
[33] Sandhu D S,Fass R.Current trends in the management of gastroesophageal reflux disease[J].Gut Liver,2018,12(1):7-16.
[34] Franceschelli S,Gatta D M P,Pesce M,et al..Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen:A new biological vision[J].J.Cell.Mol.Med.,2018,22(5):2750-2759.
[35] Johnston R D,Black G M,Harrison P W,et al..Applied sport science of australian football:A systematic review[J].Sports Med.,2018,48(7):1673-1694.
[36] 张明月.长期饮用富氢水对少年女足运动员抗氧化功能与运动机能的纵向比较研究[D].江苏苏州:苏州大学,硕士学位论文,2018.
[37] Ostojic S M,Stojanovic M D.Hydrogen-rich water affected blood alkalinity in physically active men[J].Res.Sports Med.,2014,22(1):49-60.
[38] Ishibashi T,Sato B,Rikitake M,et al..Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis:An open-label pilot study[J].Med.Gas Res.,2012,2(1):27.
[39] Nakayama M,Itami N,Suzuki H,et al..Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients:Interim analysis in a 12 month observation[J].PLoS ONE,2017,12(9):e0184535.
[40] Terawaki H,Zhu W J,Matsuyama Y,et al..Effect of a hydrogen (H2)-enriched solution on the albumin redox of hemodialysis patients[J].Hemodial.Int.,2014,18(2):459-466.
[41] Borrelli A,Bonelli P,Tuccillo F M,et al..Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma:Current and innovative therapeutic approaches[J].Redox Biol.,2018,15:467-479.
[2] Sano M,Suzuki M,Homma K,et al..Promising novel therapy with hydrogen gas for emergency and critical care medicine[J].Acute Med.Surg.,2018,5(2):113-118.
[3] Ge L,Yang M,Yang N N,et al..Molecular hydrogen:A preventive and therapeutic medical gas for various diseases[J].Oncotarget,2017,8(60):102653-102673.
[4] Dohi K,Satoh K,Miyamoto K,et al..Molecular hydrogen in the treatment of acute and chronic neurological conditions:Mechanisms of protection and routes of administration[J].J.Clin.Biochem.Nutr.,2017,61(1):1-5.
[5] 赵岭.有机磷农药生物毒性及氢保护作用的研究[D].北京:北京工业大学,博士学位论文,2013.
[6] Zhang X,Liu J,Jin K,et al..Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes[J].J.Diabetes Invest.,2018,9(1):83-90.
[7] Shang L,Xie F,Li J,et al..Therapeutic potential of molecular hydrogen in ovarian cancer[J].Transl.Cancer Res.,2018,7(4):988-995.
[8] Shao A,Wu H,Hong Y,et al..Hydrogen-rich saline attenuated subarachnoid hemorrhage-induced early brain injury in rats by suppressing inflammatory response:Possible involvement of NF-κB pathway and NLRP3 inflammasome[J].Mol.Neurobiol.,2016,53(5):3462-3476.
[9] Bedini N,Cicchetti A,Palorini F,et al..Evaluation of mediators associated with the inflammatory response in prostate cancer patients undergoing radiotherapy[J].Dis.Markers,2018,25(2):1-9.
[10] Kang K M,Kang Y N,Choi I B,et al..Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors[J].Med.Gas Res.,2011,11(1):2-8.
[11] 许长春,李燕飞,刘承军,等.富氢水防治放射性口腔粘膜反应110例临床观察[J].中国辐射卫生,27(4):363-365.
[12] Grothey A,Sobrero A F,Shields A F,et al..Duration of adjuvant chemotherapy for stage III colon cancer[J].New Engl.J.Med.,2018,378(13):1177-1188.
[13] 杨庆玺.探讨富氢水在恶性肿瘤病人化疗中的减毒增效作用[D].山东泰安:泰山医学院,硕士学位论文,2014.
[14] 郑延松,韩超进,陈志来,等.氢气对男性高尿酸血症治疗效果的研究[J].中国临床保健杂志,2017,20(2):118-121.
[15] Dai W J,Ye L,Liu A Z,et al..Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus:A meta-analysis[J].Medicine,2017,96(39):e8179.
[16] Kajiyama S,Hasegawa G,Asano M,et al..Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance[J].Nutr.Res.,2008,28(3):137-143.
[17] 周晓,钱程,吕娇,等.氢气对社区糖尿病患者氧化应激的作用及影响因素[J].社区医学杂志,2018(12):1-3.
[18] Hjort R,Ahlqvist E,Carlsson P O,et al..Overweight,obesity and the risk of LADA:Results from a Swedish case-control study and the Norwegian HUNT Study[J].Diabetologia,2018,61(6):1333-1343.
[19] Korovljev D,Trivic T,Drid P,et al..Molecular hydrogen affects body composition,metabolic profiles,and mitochondrial function in middle-aged overweight women[J].Ir.J.Med.Sci.,2018,187(1):85-89.
[20] Nasreddine L,Tamim H,Itani L,et al..A minimally processed dietary pattern is associated with lower odds of metabolic syndrome among Lebanese adults[J].Public Health Nutr.,2018,21(1):160-171.
[21] 李敏.富氢水对社区代谢综合征患者血脂及高密度脂蛋白功能的影响[D].山东泰安:泰山医学院,硕士学位论文,2013.
[22] Nakao A,Toyoda Y,Sharma P,et al..Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome—An open label pilot study[J].J.Clin.Biochem.Nutr.,2010,46(2):140-149.
[23] Song G,Li M,Sang H,et al..Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome[J].J.Lipid Res.,2013,54(7):1884-1893.
[24] Jofre-Monseny L,Minihane A M,Rimbach G.Impact of apoE genotype on oxidative stress,inflammation and disease risk[J].Mol.Nutr.Food Res.,2008,52(1):131-145.
[25] Nishimaki K,Asada T,Ohsawa I,et al..Effects of molecular hydrogen assessed by an animal model and a randomized clinical study on mild cognitive impairment[J].Curr.Alzheimer Res.,2018,15(5):482-492.
[26] Hayashida K,Sano M,Kamimura N,et al..Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management[J].Circulation,2014,130(24):2173-2180.
[27] Ono H,Nishijima Y,Ohta S,et al..Hydrogen gas inhalation treatment in acute cerebral infarction:A randomized controlled clinical study on safety and neuroprotection[J].J.Stroke Cerebrovas.Dis.,2017,26(11):2587-2594.
[28] Chen X,Cui J,Zhai X,et al..Inhalation of hydrogen of different concentrations ameliorates spinal cord injury in mice by protecting spinal cord neurons from apoptosis,oxidative injury and mitochondrial structure damages[J].Cell.Physiol.Biochem.,2018,47(1):176-190.
[29] 张哲.高浓度氢气吸入治疗脊髓损伤的基础和临床研究[D].安徽蚌埠:蚌埠医学院,硕士学位论文,2017.
[30] 漆楠楠,杨琳,李希红,等.富氢水治疗新生儿缺氧缺血性脑病疗效分析[J].泰山医学院学报,2016,37(12):1331-1332.
[31] Liu X,Yu Y,Zhu S.Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD):A meta-analysis of observational studies[J].PLoS ONE,2018,13(4):e0195659.
[32] 王如意.氢气吸入对骨科老年患者术后认知功能障碍的影响[D].天津:天津医科大学,硕士学位论文,2017.
[33] Sandhu D S,Fass R.Current trends in the management of gastroesophageal reflux disease[J].Gut Liver,2018,12(1):7-16.
[34] Franceschelli S,Gatta D M P,Pesce M,et al..Modulation of the oxidative plasmatic state in gastroesophageal reflux disease with the addition of rich water molecular hydrogen:A new biological vision[J].J.Cell.Mol.Med.,2018,22(5):2750-2759.
[35] Johnston R D,Black G M,Harrison P W,et al..Applied sport science of australian football:A systematic review[J].Sports Med.,2018,48(7):1673-1694.
[36] 张明月.长期饮用富氢水对少年女足运动员抗氧化功能与运动机能的纵向比较研究[D].江苏苏州:苏州大学,硕士学位论文,2018.
[37] Ostojic S M,Stojanovic M D.Hydrogen-rich water affected blood alkalinity in physically active men[J].Res.Sports Med.,2014,22(1):49-60.
[38] Ishibashi T,Sato B,Rikitake M,et al..Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis:An open-label pilot study[J].Med.Gas Res.,2012,2(1):27.
[39] Nakayama M,Itami N,Suzuki H,et al..Possible clinical effects of molecular hydrogen (H2) delivery during hemodialysis in chronic dialysis patients:Interim analysis in a 12 month observation[J].PLoS ONE,2017,12(9):e0184535.
[40] Terawaki H,Zhu W J,Matsuyama Y,et al..Effect of a hydrogen (H2)-enriched solution on the albumin redox of hemodialysis patients[J].Hemodial.Int.,2014,18(2):459-466.
[41] Borrelli A,Bonelli P,Tuccillo F M,et al..Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma:Current and innovative therapeutic approaches[J].Redox Biol.,2018,15:467-479.