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中华危重症医学杂志(电子版) ›› 2025, Vol. 18 ›› Issue (05) : 362 -371. doi: 10.3877/cma.j.issn.1674-6880.2025.05.002

论著

吸入性氢气通过自噬改善大鼠脊髓损伤后运动功能及神经组织修复的机制研究
茹垚钦1,2, 杨周睿1,2, 毛腾飞1,2, 张钦1,2, 潘文明3,†()   
  1. 1044000　山西运城，山西医科大学附属运城市中心医院脊柱外科
    2044000　山西运城，山西医科大学附属运城市中心医院神经医学运城市重点实验室
    3215500　江苏常熟，南通大学附属常熟医院　常熟市第二人民医院脊柱外科
  • 收稿日期:2025-07-28 出版日期:2025-10-31
  • 通信作者: 潘文明
  • 基金资助:
    江苏省常熟市科技局课题项目(CS202220); 山西省卫生健康委科研课题项目(2020168)

Mechanism of inhaled hydrogen improving motor function and neural tissue repair in rats after spinal cord injury through autophagy

Yaoqin Ru1,2, Zhourui Yang1,2, Tengfei Mao1,2, Qin Zhang1,2, Wenming Pan3,†()   

  1. 1Department of Spinal Surgery, Yuncheng Central Hospital Affiliated to Shanxi Medical University, Yuncheng 044000, China
    2Yuncheng Key Laboratory of Neuromedicine, Yuncheng Central Hospital Affiliated to Shanxi Medical University, Yuncheng 044000, China
    3Department of Spine Surgery, Affiliated Changshu Hospital of Nantong University, Changshu No.2 People's Hospital, Changshu 215500, China
  • Received:2025-07-28 Published:2025-10-31
  • Corresponding author: Wenming Pan
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引用本文：

茹垚钦, 杨周睿, 毛腾飞, 张钦, 潘文明. 吸入性氢气通过自噬改善大鼠脊髓损伤后运动功能及神经组织修复的机制研究[J/OL]. 中华危重症医学杂志(电子版), 2025, 18(05): 362-371.

Yaoqin Ru, Zhourui Yang, Tengfei Mao, Qin Zhang, Wenming Pan. Mechanism of inhaled hydrogen improving motor function and neural tissue repair in rats after spinal cord injury through autophagy[J/OL]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2025, 18(05): 362-371.

目的

探讨氢气吸入对大鼠脊髓损伤（SCI）后自噬相关蛋白表达及神经修复功能的影响。

方法

选取45只成年Sprague-Dawley雌性大鼠，采用随机数字表法分为对照组（只切除椎板）、SCI组（椎扳切除术后采用改良的Allen法造模）、氢气治疗组（SCI + H2组，采用改良的Allen法造模后给予吸入氢气处理），每组各15只。采用Basso-Beattie-Bresnahan（BBB）评分对各组大鼠SCI后1、3、7、14、21、28 d后肢运动功能进行评估。利用苏木素-伊红（HE）染色观察脊髓前角与损伤部位组织的结构和形态变化；利用尼氏染色观察脊髓神经元形态学变化。采用western-blotting检测SCI后各组大鼠脊髓组织磷脂酰肌醇3激酶（PI3K）、蛋白激酶B（Akt）、磷酸化Akt（p-Akt）、哺乳动物雷帕霉素靶蛋白（mTOR）、磷酸化mTOR（p-mTOR）蛋白表达水平。通过免疫荧光染色对SCI后各组大鼠微管相关蛋白1轻链3（LC3）、Beclin-1、胶质纤维酸性蛋白（GFAP）、微管相关蛋白2（MAP2）、髓鞘碱性蛋白（MBP）、Tuj-1水平进行检测。

结果

3组大鼠建模后1、3、7、14、21、28 d的BBB评分比较差异均有统计学意义（F = 4 805.000、571.200、323.400、134.400、62.740、28.720，P均< 0.001），且在建模后21、28 d，SCI + H2组的BBB评分较SCI组均显著增加（P均< 0.05）。HE染色可见对照组脊髓结构完整，SCI组出现明显组织空洞与神经元缺失，SCI + H2组损伤程度较SCI组有明显改善。尼氏染色结果显示，SCI + H2组尼氏小体数量较SCI组显著增加，但较对照组减少。Western-blotting结果显示，3组大鼠p-mTOR/mTOR（F = 17.030，P = 0.006）、p-Akt/Akt（F = 13.000，P = 0.004）比值比较，差异均有统计学意义；且SCI + H2组及对照组大鼠中p-mTOR/mTOR、p-Akt/Akt比值均显著高于SCI组（P均< 0.05）。而3组大鼠间PI3K比较差异无统计学意义（F = 0.267，P = 0.861）。免疫荧光染色显示，3组大鼠GFAP（F = 181.100，P = 0.001）、MAP2（F = 264.800，P = 0.005）、MBP（F = 239.800，P = 0.001）、Tuj-1（F = 105.400，P = 0.001）、LC3（F = 105.500，P = 0.001）、Beclin-1（F = 39.530，P = 0.003）平均荧光强度比较，差异均有统计学意义；且与SCI组大鼠比较，SCI + H2组的GFAP、LC3、Beclin-1平均荧光强度均显著降低（P均< 0.05），MAP2、MBP、Tuj-1的平均荧光强度均显著升高（P均< 0.05）。

结论

氢气吸入可通过抑制SCI后过度的自噬反应，促进神经组织修复相关蛋白表达，从而改善大鼠运动功能恢复。

关键词: 脊髓损伤, 氢气, 自噬, 神经修复
Objective

To investigate the effects of hydrogen inhalation on the expression of autophagy-related proteins and neural repair function in rats after spinal cord injury (SCI).

Methods

Forty-five female Sprague-Dawley rats were selected and divided into three groups using a random number table method, with 15 rats in each group: the control group (treated with only lamina resection), the SCI group (treated with a modified Allen method for modeling after laminectomy), and the hydrogen treatment group (SCI + H2 group, given hydrogen inhalation after modeling). The Basso-Beattie-Bresnahan (BBB) score was used to evaluate the hind limb motor function of rats in each group at 1, 3, 7, 14, 21, and 28 days after SCI. Hematoxylin-eosin (HE) staining was used to observe the structural and morphological changes of the anterior horn of the spinal cord and the tissue at the injury site; Nissl staining was used to observe the morphological changes of spinal cord neurons. The protein expression levels of phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) in the spinal cord tissue of rats in each group after SCI were detected by western-blotting. The levels of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), myelin basic protein (MBP), and Tuj-1 of rats in each group after SCI were detected by immunofluorescence staining.

Results

There were significant differences in the BBB scores of the three groups at 1, 3, 7, 14, 21, and 28 days after modeling (F = 4 805.000, 571.200, 323.400, 134.400, 62.740, 28.720, all P < 0.001), and at 21 and 28 days after modeling, the BBB scores in the SCI + H2 group were significantly higher than those in the SCI group (both P < 0.05). HE staining revealed that the spinal cord structure of the control group was intact, while obvious tissue cavities and neuronal loss occurred in the SCI group. The injury degree of the SCI + H2 group was significantly improved compared with the SCI group. The Nissl staining showed that the number of Nissl bodies in the SCI + H2 group was significantly increased compared with the SCI group, but was less than that in the control group. Western-blotting showed that there were significant differences in the ratios of p-mTOR/mTOR (F = 17.030, P = 0.006) and p-AKT/Akt (F = 13.000, P = 0.004) among the three groups. Moreover, the ratios of p-mTOR/mTOR and p-AKT/Akt in the SCI + H2 group and the control group were much higher than those in the SCI group (all P < 0.05). However, there was no statistically significant difference in the PI3K expression among the three groups (F = 0.267, P = 0.861). The immunofluorescence staining indicated that in the three groups, the average fluorescence intensities of GFAP (F = 181.100, P = 0.001), MAP2 (F = 264.800, P = 0.005), MBP (F = 239.800, P = 0.001), Tuj-1 (F = 105.400, P = 0.001), LC-3 (F = 105.500, P = 0.001), and Beclin-1 (F = 39.530, P = 0.003) all showed statistically significant differences. Moreover, compared with the SCI group, the average fluorescence intensities of GFAP, LC3, and Beclin-1 in the SCI + H2 group were significantly decreased, while the average fluorescence intensities of MAP2, MBP, and Tuj-1 were significantly increased (all P < 0.05).

Conclusion

Hydrogen inhalation can improve the recovery of motor function in rats after SCI by inhibiting the excessive autophagy response and promoting the expression of proteins related to neural tissue repair.

Key words: Spinal cord injury, Hydrogen, Autophagy, Neural repair
图1 3组大鼠在不同时间点的BBB评分比较（每组n = 6）注：BBB. Basso-Beattie-Bresnahan；SCI.脊髓损伤；H2.氢气
图2 3组大鼠脊髓损伤后28 d的足迹图注：蓝、红墨水分别为大鼠前后肢的足迹；SCI.脊髓损伤；H2.氢气
图3 SCI后3组大鼠脊髓组织的HE染色结果图注：SCI.脊髓损伤；HE.苏木素-伊红；H2.氢气；a ~ c图为脊髓组织的前角病理图，SCI + H2组神经元数量较SCI组增多，细胞形态更规则，组织损伤有所缓解，但神经元数量、组织紧密性等仍未完全恢复至对照组的正常水平；d ~ f图为脊髓组织的损伤部位，SCI + H2组神经元数量较SCI组增多，细胞形态更规则，组织疏松、损伤程度较SCI组明显减轻，但还未恢复至对照组水平（HE染色　× 200）
图4 SCI后3组大鼠脊髓组织神经元的尼氏染色结果图注：SCI.脊髓损伤；H2.氢气；SCI + H2组神经元数量较SCI组增多，细胞形态更饱满、规则，尼氏小体更丰富，但未完全恢复至对照组的正常水平（尼氏染色　× 200）
图5 SCI后3组大鼠GFAP、MAP2、MBP、Tuj-1免疫荧光强度的比较（每组n = 3）注：SCI.脊髓损伤；GFAP.胶质纤维酸性蛋白；MAP2.微管相关蛋白2；MBP.髓鞘碱性蛋白；DAPI. 4',6-二脒基-2-苯基吲哚；H2.氢气；与对照组比较，aP < 0.05；与SCI组比较，bP < 0.05（免疫荧光染色　× 400）
图6 SCI后3组SCI大鼠p-mTOR/mTOR、p-Akt/Akt及PI3K蛋白表达的比较（每组n = 3）注：SCI.脊髓损伤；p-mTOR.磷酸化雷帕霉素靶蛋白；p-Akt.磷酸化蛋白激酶B；PI3K.磷脂酰肌醇3激酶；GAPDH.甘油醛-3-磷酸脱氢酶；H2.氢气；与对照组比较，aP < 0.05；与SCI组比较，bP < 0.05
图7 SCI后3组大鼠LC3、Beclin-1的免疫荧光染色情况（每组n = 3）注：SCI.脊髓损伤；LC3.微管相关蛋白1轻链3；NeuN.神经元核心；DAPI. 4',6-二脒基-2-苯基吲哚；H2.氢气；与对照组比较，aP < 0.05；与SCI组比较，bP < 0.05（免疫荧光染色　× 400）
1
Guérout N. Plasticity of the injured spinal cord[J]. Cells, 2021, 10 (8): 1886.
2
Devivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications[J]. Spinal Cord, 2012, 50 (5): 365-372.
3
GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet Neurol, 2019, 18 (1): 56-87.
4
Zhai X, Chen K, Wei X, et al. Microneedle/CD-MOF-mediated transdural controlled release of methylprednisolone sodium succinate after spinal cord injury[J]. J Control Release, 2023, 360: 236-248.
5
Adegeest CY, Ter Wengel PV, Peul WC. Traumatic spinal cord injury: acute phase treatment in critical care[J]. Curr Opin Crit Care, 2023, 29 (6): 659-665.
6
吴鑫杰，谭明生，移平. NOD样受体蛋白3炎性小体在创伤性脊髓损伤中的作用[J].中医正骨，2019，31（2）：31-35.
7
Hu X, Xu W, Ren Y, et al. Spinal cord injury: molecular mechanisms and therapeutic interventions[J]. Signal Transduct Target Ther, 2023, 8 (1): 245.
8
Wu J, Lipinski MM. Autophagy in neurotrauma: good, bad, or dysregulated[J]. Cells, 2019, 8 (7): 693.
9
Pukos N, Marion CM, Arnold WD, et al. Chronic demyelination and myelin repair after spinal cord injury in mice: a potential link for glutamatergic axon activity[J]. Glia, 2023, 71 (9): 2096-2116.
10
Hu X, Xu W, Ren Y, et al. Spinal cord injury: molecular mechanisms and therapeutic interventions[J]. Signal Transduct Target Ther, 2023, 8 (1): 245.
11
Buzoianu-Anguiano V, Torres-Llacsa M, Doncel-Pérez E. Role of aldynoglia cells in neuroinflammatory and neuroimmune responses after spinal cord injury[J]. Cells, 2021, 10 (10): 2783.
12
An N, Yang J, Wang H, et al. Mechanism of mesenchymal stem cells in spinal cord injury repair through macrophage polarization[J]. Cell Biosci, 2021, 11 (1): 41.
13
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.
14
尚云，王倩楠，申英俊，等.氢气对大鼠缺氧缺血性脑病的抗炎和神经保护作用[J].医学研究志，2025，54（3）：80-84.
15
Chu X, Cao L, Yu Z, et al. Hydrogen-rich saline promotes microglia M2 polarization and complement-mediated synapse loss to restore behavioral deficits following hypoxia-ischemic in neonatal mice via AMPK activation[J]. J Neuroinflammation, 2019, 16 (1): 104.
16
肖琦凡，康曼德，唐彬，等.氢气对神经系统疾病治疗作用的研究进展[J].重庆医学，2022，51（18）：3217-3220.
17
Wang F, Zhang G, Zhai Q. Role and mechanism of molecular hydrogen in the treatment of Parkinson's diseases[J]. Front Neurosci, 2025, 19: 1576773.
18
Zhang YG, Sheng QS, Wang ZJ, et al. Hydrogen-rich saline promotes motor functional recovery following peripheral nerve autografting in rats[J]. Exp Ther Med, 2015, 10 (2): 727-732.
19
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.
20
Chen L, Chao Y, Cheng P, et al. UPLC-QTOF/MS-based metabolomics reveals the protective mechanism of hydrogen on mice with ischemic stroke[J]. Neurochem Res, 2019, 44 (8): 1950-1963.
21
吴杰，周志强，符菁，等.吸入性氢气对大鼠脊髓损伤后自噬及神经功能的影响[J/OL].中华危重症医学杂志（电子版），2024，17（5）：363-371.
22
Alizadeh A, Dyck SM, Karimi-Abdolrezaee S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms[J]. Front Neurol, 2019, 10: 282.
23
Ahuja CS, Wilson JR, Nori S, et al. Traumatic spinal cord injury[J]. Nat Rev Dis Primers, 2017, 3: 17018.
24
Li H, Sun H, Li S, et al. Hydrogen alleviates hypoxic-ischaemic brain damage in neonatal rats by inhibiting injury of brain pericytes[J]. J Cell Mol Med, 2024, 28 (13): e18505.
25
Yuan J, Wang D, Liu Y, et al. Hydrogen-rich water attenuates oxidative stress in rats with traumatic brain injury via Nrf2 pathway[J]. J Surg Res, 2018, 228: 238-246.
26
陈含冰，储翠林，邱海波.急性呼吸窘迫综合征中巨噬细胞死亡方式的研究进展[J/OL].中华重症医学电子杂志，2024，10（1）：79-84.
27
田昊哲，郑娟，王晓璇，等.自噬在脊髓损伤中的生物学功能和治疗潜力[J].中国现代医生，2025，63（6）：110-114.
28
Liu Y, Leng B, Xia M, et al. Regulatory role of the mTOR signaling pathway in autophagy and mesangial proliferation in IgA nephropathy[J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2024, 49 (8): 1220-1231.
29
Deleyto-Seldas N, Efeyan A. The mTOR-autophagy axis and the control of metabolism[J]. Front Cell Dev Biol, 2021, 9: 655731.
30
Zhang Q, Wang X, Cao S, et al. Berberine represses human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt signaling pathways[J]. Biomed Pharmacother, 2020, 128: 110245.
31
Rubinsztein DC, Codogno P, Levine B. Autophagy modulation as a potential therapeutic target for diverse diseases[J]. Nat Rev Drug Discov, 2012, 11 (9): 709-730.
32
Xiao P, Gu J, Xu W, et al. RTN4/Nogo-A-S1PR2 negatively regulates angiogenesis and secondary neural repair through enhancing vascular autophagy in the thalamus after cerebral cortical infarction[J]. Autophagy, 2022, 18 (11): 2711-2730.
33
Peng W, Wan L, Luo Z, et al. Microglia-derived exosomes improve spinal cord functional recovery after injury via inhibiting oxidative stress and promoting the survival and function of endothelia cells[J]. Oxid Med Cell Longev, 2021: 1695087.
34
Clifford T, Finkel Z, Rodriguez B, et al. Current advancements in spinal cord injury research—glial scar formation and neural regeneration[J]. Cells, 2023, 12 (6): 853.
35
Yang RY, Chai R, Pan JY, et al. Knockdown of polypyrimidine tract binding protein facilitates motor function recovery after spinal cord injury[J]. Neural Regen Res, 2023, 18 (2): 396-403.
36
Stern S, Hilton BJ, Burnside ER, et al. RhoA drives actin compaction to restrict axon regeneration and astrocyte reactivity after CNS injury[J]. Neuron, 2021, 109 (21): 3436-3455.e9.
37
Zheng B, Tuszynski MH. Regulation of axonal regeneration after mammalian spinal cord injury[J]. Nat Rev Mol Cell Biol, 2023, 24 (6): 396-413.
38
Bai X, Liu S, Yuan L, et al. Hydrogen-rich saline mediates neuroprotection through the regulation of endoplasmic reticulum stress and autophagy under hypoxia-ischemia neonatal brain injury in mice[J]. Brain Res, 2016, 1646: 410-417.
39
Cheng M, Gao Y, Wu Y, et al. Plasmalogens activate AKT/mTOR signaling to attenuate reactive oxygen species production in spinal cord injury[J]. Curr Gene Ther, 2025. Online ahead of print.
40
Li GL, Farooque M, Holtz A, et al. Microtubule-associated protein 2 as a sensitive marker for dendrite lesions after spinal cord trauma: an immunohistochemical study in the rat[J]. Restor Neurol Neurosci, 1995, 8 (4): 189-197.
41
Weng J, Wang L, Wang K, et al. Correction: tauroursodeoxycholic acid inhibited apoptosis and oxidative stress in H2O2-induced bmsc death via modulating the Nrf-2 signaling pathway: the therapeutic implications in a rat model of spinal cord injury[J]. Mol Neurobiol, 2024, 61 (7): 3769-3770.
42
杨永祥.外泌体源性miR-124对创伤性脑损伤后海马区神经炎症和神经再生的作用和机制研究[D].西安：中国人民解放军空军军医大学，2019.
43
Deryugina AV, Danilova DA, Pichugin VV, et al. The effect of molecular hydrogen on functional states of erythrocytes in rats with simulated chronic heart failure[J]. Life (Basel), 2023, 13 (2): 418.
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