硫化氢治疗急性肺损伤的研究进展

doi:10.16352/j.issn.1001-6325.2026.04.0592

摘要/Abstract

摘要： 硫化氢(H₂S)作为一种气体信号分子,可明显缓解急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS),延缓疾病发展进程。硫化氢通过抗炎、抗氧化作用抑制促炎因子释放、减轻氧化应激;调控细胞凋亡、自噬、焦亡、铁死亡等多种细胞死亡方式减轻肺组织损伤;维持肺血管内皮屏障完整性,减轻肺组织水肿。此外,硫化氢可通过硫氢化修饰调控相关蛋白的活性,发挥肺保护作用。

关键词: 硫化氢, 肺炎, 脓毒血症, 急性肺损伤

Abstract: Hydrogen sulfide (H₂S), as a gaseous signaling molecule, can significantly alleviate acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and delay disease progression. H₂S exerts its effects by suppressing the release of pro-inflammatory factors and reducing oxidative stress through its anti-inflammatory and antioxidant properties; it mitigates lung tissue damage by regulating various forms of cell death, including apoptosis, autophagy, pyroptosis, and ferroptosis; and it maintains the integrity of the pulmonary vascular endothelial barrier, thereby reducing pulmonary edema. Additionally, H₂S can modulate the activity of related proteins via sulfhydration, contributing to its lung-protective effects.

Key words: hydrogen sulfide, pneumonia, sepsis, acute lung injury

中图分类号:

R563

朱敏, 唐苗苗. 硫化氢治疗急性肺损伤的研究进展[J]. 基础医学与临床, 2026, 46(4): 592-596.

ZHU Min, TANG Miaomiao. Advances in hydrogen sulfide therapy for acute lung injury[J]. Basic & Clinical Medicine, 2026, 46(4): 592-596.

参考文献

[1] Atefi N, Goodarzi A, Riahi T, et al. Evaluation of the efficacy and safety of oral N-acetylcysteine in patients with COVID-19 receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled clinical trial[J]. Immun Inflamm Dis, 2023, 11:e1083. doi: 10.1002/iid3.1083.
[2] Star BS, Van Der Slikke EC, Ransy C, et al. GYY4137-derived hydrogen sulfide donates electrons to the mitochondrial electron transport chain via sulfide: quinone oxidoreductase in endothelial cells[J]. Antioxidants, 2023, 12:587. doi: 10.3390/antiox12030587.
[3] Melo ISF, Ziviani VP, Barbosa BCM, et al. Synthesis of 2-(2-(4-thioxo-3H-1,2-dithiole-5-yl) phenoxy)ethyl)isoindole-1,3-thione, a novel hydrogen sulfide-releasing phthalimide hybrid, and evaluation of its activity in models of inflammatory pain[J]. Eur J Pharmacol, 2023, 938: 175409. doi: 10.1016/j.ejphar.2022.175409.
[4] He Y, Gang B, Zhang M, et al. ACE2 improves endothelial cell function and reduces acute lung injury by downregulating FAK expression[J]. Int Immunopharmacol, 2024, 128: 111535. doi: 10.1016/j.intimp.2024.111535.
[5] Lin M, Lin C, Chang J, et al. The influence of PM2.5 exposure on SARS-CoV-2 infection via modulating the expression of angiotensin converting enzyme II[J]. J Hazard Mater, 2025, 485: 136887. doi: 10.1016/j.jhazmat.2024.136887.
[6] Lin Y, Zeng H, Gao L, et al. Hydrogen sulfide attenuates atherosclerosis in a partially ligated carotid artery mouse model via regulating angiotensin converting enzyme 2 expression[J]. Front Physiol, 2017, 8: 782. doi: 10.3389/fphys.2017.00782.
[7] Gyebi GA, Adegunloye AP, Ibrahim IM, et al. Prevention of SARS-CoV-2 cell entry: insight from in silico interaction of drug-like alkaloids with spike glycoprotein, human ACE2, and TMPRSS2[J]. J Biomol Struct Dyn, 2022, 40: 2121-2145. doi: 10.1080/07391102.2020.1835726.
[8] Escaffre O, Szaniszlo P, Törö G, et al. Hydrogen sulfide ameliorates SARS-CoV-2-associated lung endothelial barrier disruption[J]. Biomedicines, 2023, 11:1790. doi: 10.3390/biomedicines11071790.
[9] Gjuzelova AA, Nakova VV, Nanovic Z, et al. Association of inflammatory markers with disease severity and outcome in covid-19 patients[J]. Pril (Makedon Akad Nauk Umet Odd Med Nauki), 2023, 44: 89-95. doi: 10.2478/prilozi-2023-0010.
[10] Zimmermann KK, Spassov SG, Strosing KM, et al. Hydrogen sulfide exerts anti-oxidative and anti-inflammatory effects in acute lung injury[J]. Inflammation, 2018, 41: 249-259. doi: 10.1007/s10753-017-0684-4.
[11] Jiang L, Jiang Q, Yang S, et al. GYY4137 attenuates LPS-induced acute lung injury via heme oxygenase-1 modulation[J]. Pulm Pharmacol Ther, 2019, 54: 77-86. doi: 10.1016/j.pupt.2018.12.004.
[12] Xu X, Li H, Gong Y, et al. Hydrogen sulfide ameliorated lipopolysaccharide-induced acute lung injury by inhibiting autophagy through PI3K/Akt/mTOR pathway in mice[J]. Biochem Biophys Res Commun, 2018, 507: 514-518. doi: 10.1016/j.bbrc.2018.11.081.
[13] Faller S, Hausler F, Goeft A, et al. Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury[J]. Sci Rep, 2018, 8:14676. doi: 10.1038/s41598-018-33101-x.
[14] 周晓红,黄新莉,韦鹏,等.硫化氢/胱硫醚-γ-裂解酶在内毒素性急性肺损伤发生中的作用[J].中国危重病急救医学,2009,21:199-202.
[15] 王平,张建新,巩建平,等.硫化氢对大鼠内毒素性急性肺损伤肺泡表面活性物质的影响[J].中国应用生理学杂志,2011,27:485-489.
[16] Du Q, Wang C, Zhang N, et al. In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats[J]. BMC Anesthesiol, 2014, 14: 117. doi: 10.1186/1471-2253-14-117.
[17] Zhu M, Fan X, Zhang N, et al. Endothelial endog-enous CSE/H₂S inhibits endothelial pyroptosis by activating sirtuin1 to attenuate LPS-induced acute lung injury[J]. FASEB J, 2025, 39: e70420. doi: 10.1096/fj.202402042R.
[18] Qian H, Chen Q. Hydrogen sulfide modulates acute lung injury in sepsis by inhibiting NLRP3 inflammasome activation in mice[J]. Chin J Tuberc Respir Dis, 2025, 48: 130-137. doi: 10.3760/cma.j.cn112147-20240718-00413.
[19] Qin Y, Li W, Liu J, et al. Andrographolide ameliorates sepsis-induced acute lung injury by promoting autophagy in alveolar macrophages via the RAGE/PI3K/AKT/mTOR pathway[J]. Int Immunopharmacol, 2024, 139: 112719. doi: 10.1016/j.intimp.2024.112719.
[20] Cao Z, Qin H, Huang Y, et al. Crosstalk of pyroptosis, ferroptosis, and mitochondrial aldehyde dehydrogenase 2-related mechanisms in sepsis-induced lung injury in a mouse model[J]. Bioengineered, 2022, 13: 4810-4820. doi: 10.1080/21655979.2022.2033381.
[21] Li J, Li M, Li L, et al. Hydrogen sulfide attenuates ferroptosis and stimulates autophagy by blocking mTOR signaling in sepsis-induced acute lung injury[J]. Mol Immunol, 2022, 141: 318-327. doi: 10.1016/j.molimm.2021.12.003.
[22] Linao S, Haoran Y, Hao F, et al. The role and mechan-ism of PDZ binding kinase in hypobaric and hypoxic acute lung injury[J]. J Thorac Dis, 2024, 16:2082-2102. doi: 10.21037/jtd-24-188.
[23] Wang R, Ma S, Yang J, et al. Sodium hydrosulfide protects rats from hypobaric-hypoxia-induced acute lung injury[J]. Int J Mol Sci, 2024, 25:10734. doi: 10.3390/ijms251910734.
[24] Spassov SG, Donus R, Ihle PM, et al. Hydrogen sulfide prevents formation of reactive oxygen species through PI3K/Akt signaling and limits ventilator-induced lung injury[J]. Oxid Med Cell Longev, 2017, 2017:3715037. doi: 10.1155/2017/3715037.
[25] Francis RC, Vaporidi K, Bloch KD, et al. Protective and detrimental effects of sodium sulfide and hydrogen sulfide in murine ventilator-induced lung injury[J]. Anesthesiology, 2011, 115: 1012-1021. doi: 10.1097/ALN.0b013e31823306cf.