硫化氢在中枢神经系统疾病中的作用研究进展

神经药理学报 ›› 2014, Vol. 4 ›› Issue (3): 49-56.

硫化氢在中枢神经系统疾病中的作用研究进展

李国风, 骆海坤, 张建新

1. 河北省疾病预防控制中心药物研究所，石家庄，050021，中国
2. 河北省邢台市第三医院药剂科，邢台，054000，中国

出版日期:2014-06-26 发布日期:2015-01-20
通讯作者: 张建新，男，研究员，博士，博士生导师；研究方向：心脑血管药理学；Tel：+86-0311-86573288，E-mail:zhangjx100@163.com
作者简介:李国风，男，博士；研究方向：心脑血管药理学；Tel：+86-0311-86573410，E-mail：guofengli1979@sina.com
基金资助:
河北省自然科学基金 (C2009001458)；河北省自然科学基金(H2014303005)；河北省重点基础研究项目(13967602D)；河北省卫生厅医学研究重点课题（20111024）

Research Progress on the Role of Hydrogen Sulfide in the Central Nervous System

LI Guo-feng, LUO Hai-kun, ZHANG Jian-xin

Institute of Materia Medical, Hebei Province Center for Disease Prevention and Control, Shi jia zhuang, 050021, Hebei, China

Online:2014-06-26 Published:2015-01-20
Contact: 张建新，男，研究员，博士，博士生导师；研究方向：心脑血管药理学；Tel：+86-0311-86573288，E-mail:zhangjx100@163.com
About author:李国风，男，博士；研究方向：心脑血管药理学；Tel：+86-0311-86573410，E-mail：guofengli1979@sina.com
Supported by:
河北省自然科学基金 (C2009001458)；河北省自然科学基金(H2014303005)；河北省重点基础研究项目(13967602D)；河北省卫生厅医学研究重点课题（20111024）

摘要/Abstract

摘要： 硫化氢（hydrogen sulfide，H2S）是继一氧化氮（nitric oxide，NO）和一氧化碳（carbon monoxide，CO）之后的第三种气体信号分子，其在体内由特殊的酶催化产生，有其特殊的代谢过程。其在中枢神经系统中发挥着重要的作用，在生理状态下参与海马长时程增强、神经胶质细胞作用的发挥，通过影响下丘脑-垂体-肾上腺轴而影响神经内分泌过程，参与神经元氧化应激反应和脑血管功能的调节；H2S还参与多种中枢神经系统疾病如阿尔默茨病、热性惊厥、唐氏综合症、脑缺血、脑缺血再灌注等的病理生理过程。本文就H2S在中枢神经系统的研究概况做综述如下。

关键词: 硫化氢, 中枢神经系统, 脑缺血, 作用机制

Abstract: Hydrogen sulfide (H2S) is the third gas signal molecule followed by nitric oxide (NO) and carbon monoxide (CO), which is produced by special enzyme catalysis in the body and has specific metabolic process. It plays an important role in the central nervous system. It participates in many nervous functions such as long-term potentiation of hippocampus and the role of the glial cell activity. It impacts the hypothalamus - pituitary - adrenal axis, participates in the regulation of neuronal oxidative stress reaction and cerebrovascular function in the physiologicalstate. It is also involved in a variety of central nervous system diseases such as Alzheimer's disease, head-induced seizure, Down syndrome, and the pathophysiological processes of cerebral ischemia and cerebral ischemia reperfusion. In this paper, we reviewed the research progress of H2S in the central nervous system.

Key words: Hydrogen sulfide, Central nervous system, cerebral ischemia, mechanisms

中图分类号:

R964

李国风, 骆海坤, 张建新. 硫化氢在中枢神经系统疾病中的作用研究进展[J]. 神经药理学报, 2014, 4(3): 49-56.

LI Guo-feng, LUO Hai-kun, ZHANG Jian-xin. Research Progress on the Role of Hydrogen Sulfide in the Central Nervous System[J]. Acta Neuropharmacologica, 2014, 4(3): 49-56.

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[1] 蒋元强，姜永根，孙中兴. 一起硫化氢中毒死亡事故调查[J]. 职业卫生与应急救援，2013，31(6): 306-307.

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[3] Goodwin L R, Francom D, Dieken F P, et al. Determination of sulfide in brain tissue by gas dialysis/ion chromatography: postmortem studies and two casereports[J]. J Anal Toxicol, 1989, 13(2): 105-109.

[4] Kazuho Abe, Hideo Kimura. The possible role of hydrogen sulfide as an endogenous neuromodulator[J]. Neurosci, 1996, 16(3): 1066-1071.

[5] Zhang Xing-zhou, Jin-song S Bian. Hydrogen sulfide: a neuromodulator and neuroprotectant in the central nervous system [J]. ACS Chem Neurosci, 2014, 5(10): 876-883.

[6] Kamoun P. Endogenous production of hydrogen sulfide in mammals[J]. Amino Aeiels, 2004, 26(3): 243-254.

[7] 刘芳，刘广杰，张建新，等. 外源性硫化氢对大鼠急性心肌缺血损伤时炎性反应的影响[J]. 中华麻醉学杂志, 2014, 34(2): 227-229.

[8] Hideo Kimura. Hydrogen sulfide: from brain to gut[J]. Antioxid Redox Signal, 2010, 12(9): 1111-1123.

[9] Norihiro Shibuya, Makiko Tanaka, Mikiharu Yoshida, et al. 3-Mercaptopyruvate sulfur Transferase produces hydrogen sulfide and bound sulfane sulfur in the brain[J]. Antioxid Redox Signal, 2009, 11(4): 703-714.

[10] Ko Eto, Hideo Kimura. The production of hydrogen sulfide is regulated by testosterone and S-adenosyl-L-methionine in mouse brain [J]. J Neurochem, 2002, 83 (1): 80-86.

[11] Bao Li-ming, Cestmi Vleek, Vaclav Paces, et al. Idetification and tissue distribution of human cystathionine beta-synthase mRNA isoforms[J]. Arch Biochem Biophys, 1998, 350 (1): 95-103.

[12] Caroline J Richardson, Elizabeth A M Magee, John H Cwmmings. A new method for the determination of sulphide in gastrointestinal contents and whole blood by microdistillation and ion chromatography[J]. Clin Chim Acta, 2000, 293 (1-2): 115-125.

[13] Bang Rui. The gasotransmitter role of hydrogen sulfide[J]. Antioxid Redox Sianal, 2003, 5(4): 493-501.

[14] Julie Furne, Aalia Saeed, Michael D Levitt. Whole tissue hydrogen sulfide concentr-ations are orders ofmagnitude lower than presently accepted values[J]. Am J Physiol Regul Integr Comp Physiol, 2008, 295(5): 1479-1485.

[15] Ogasawara Y, Ishii K, Togawa T, et al. Determination of bound sulfur in serum by gas dialysis/high-performance liquid chromatography[J]. Anal Biochem, 1993, 215(1): 73-81.

[16] Toohey J I. Sulphane sulphur in biological systems: A possible regulatory role[J]. Biochem J, 1989, 264(3): 625-632.

[17] Wang Rui. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? [J]. FASEB, 2002, 16(13): 1792- 1798.

[18] Martha H Stipanuk. Sulfuramino acid metabolism pathways for production and removal of homocysteine and cysteine[J]. Annu Rev Nutr, 2004, 24:539-577.

[19] Ko Eto, Miki Ogasawara, Ken Umemura, et al. Hydrogen sulfide is produced in response to neuronal excitation[J]. J Neurosci, 2002, 22(9): 3386-3391.

[20] Moonhee Lee, Claudia Schwab, Yu Sheng, et al. Astrocytes produce the anti-inflammatary and neuroprotective agent hydrogen sulfide[J]. Neurobiol Aging, 2009, 30 (10): 1523-1534.

[21] Yasushi Enokido, Eri Suzuki, Kazu Iwasawa, et al. Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse[J]. FASEB J, 2009, 19 (13): 1854-1856.

[22] Shiau Wei Lee, Yvonne Cheng, Philip K Moore, et al. Hydrogen sulphide regulates intra- cellular pH in vascular smooth muscle cells[J]. Biochem Biophys Res Commun, 2007, 358(4): 1142-1147.

[23] Lu Ming, Chooi Hoong Choo, Hu Li-fang, et al. Hydrogen sulfide regulates intracellular pH in ratprimary cultured glia cells[J]. Neurosci Res, 2010, 66(1): 92-98.

[24] 代政伟, 晏勇, 张华, 等. 硫化氢与神经胶质细胞功能的研究进展[J]. 中国老年学杂志, 2011, 31(3): 1072-1074.

[25] Yasuo Nagai, Mamiko Tsugane, Jun-Ichiro Oka, et al. Hydrogen sulfide induces calcium waves in astrocytes[J]. FASEB J, 2004, 18(3): 557-559.

[26] Shiau Wei Lee, Ye-Shi Hu, Hu Li-fang, et al. Hydrogen sulphide regulates calcium homeostasis inmicroglial cells[J]. Glia, 2009, 54(2): 116-124.

[27] Oh Gi-su, Pae Hyun-Ock, Lee Bok-Soo, et al. Hydrogen sulfide inhibits nitric oxide production and nuclear factor-kappaB via hemeoxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide[J]. Free Radic BiolMed, 2006, 41(1): 106-119.

[28] Ki Kyung Jung, Hae Sung Lee, Jae Youl Cho, et al. Inhibitory effect of curcumin on nitricoxide production from lipopolysaccharide-activated primary microglia[J]. Life Sci, 2006, 79(21): 2022-2031.

[29] Laura Rinaldi, Giuliana Gobbi, Maurizia Pambianco, et al. Hydrogen sulphide prevents apoptosis of human PMN via inhibition of p38 and caspase 3[J]. Lab Invest, 2006, 86(4): 391-397.

[30] Dello Russo C, Tringali G, Ragazzoni E, et al. Evidence that hydrogen sulphide can modulate hypothalamo-pituitary-adrenal axis function: in vitro and in vivo studies in the rat[J]. J Neuroendocrinol, 2000, 12(3): 225-233.

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