Neuroprotective effect of exogenous hydrogen sulfide and the expression of matrix metalloproteinases-9 and Caspase-1 in mice model of Parkinson’s disease

doi:10.16098/j.issn.0529-1356.2023.03.006

Abstract

Abstract:

Objective To investigate the protective effect of exogenous hydrogen sulfide (H2S) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinson’s disease in mice and the effect on the expression of matrix metalloproteinase-9 (MMP-9) and Caspase-1. Methods Totally 36 male Kunming mice were randomly divided into control group, PD group and PD+sodium hydrosulfide(NaHS) group, with 12 mice in each group. PD group was intraperitoneally injected with MPTP (30 mg/kg), once a day, for 7 consecutive days to induce Parkinson’s disease mouse model. PD+NaHS group was intraperitoneally injected with 5.6 mg/kg NaHS(donors of H₂S) 30 minutes before modeling，and control group was given the same amount of normal saline. The behavioral changes of mice were evaluated by tremor paralysis score and suspension test, and the morphological changes of neurons in the substantia nigra (SN) were observed by HE staining. The expressions of tyrosine hydrogenase (TH), MMP-9 and Caspase-1 in the SN were detected by immunohistochemistry and Western blotting. Results Compared with the control group, the score of tremor paralysis in PD group increased (P<0.05), and the score of suspension test decreased (P<0.05). Under the light microscope, the number of neurons in the SN decreased significantly, and the arrangement was disordered. The number of TH positive cells and TH protein expression in the SN decreased (P<0.05), while the number of MMP-9 and Caspase-1 positive cells and the expression levels of MMP-9 and Caspase-1 increased (P<0.05). Compared with the PD group, the tremor paralysis score in PD+NaHS group decreased (P<0.05), the suspension test score increased (P<0.05), and the number of neurons in the SN increased significantly. The number of TH positive cells and TH protein expression levels in the SN increased (P<0.05), while the number of MMP-9 and Caspase-1 positive cells and the expression levels of MMP-9 and Caspase-1 decreased (P<0.05). Conclusion Exogenous hydrogen sulfide has a protective effect on dopaminergic neurons in the SN of PD mice, which might be related to the inhibition of MMP-9 and Caspase-1 mediated neuroinflammatory response.

Key words:

Hydrogen sulfide, Parkinson’s disease, Matrix metalloproteinases-9, Caspase-1, Immunohistochemistry, Western blotting, Mouse

CLC Number:

R364.5

LIU Ke-ting CHEN Bin-bin SHUI Yu-lian SHI Qing-ming XIAO Li. Neuroprotective effect of exogenous hydrogen sulfide and the expression of matrix metalloproteinases-9 and Caspase-1 in mice model of Parkinson’s disease[J]. Acta Anatomica Sinica, 2023, 54(3): 289-295.

References

［1］Wang TT，Chen ZhCh，Ye X，et al. Allopregnanolone restores dopaminergic neurons and motor performance in Parkinson’s disease mice and its molecular mechanisms ［J］.Acta Anatomica Sinica，2020，51（4）：473-482.（in Chinese）

王彤彤，陈治池，叶鑫，等.别孕烯醇酮对帕金森病模型小鼠黑质多巴胺能神经元的影响及可能的分子机制［J］. 解剖学报，2020，51（4）：473-482.

［2］Mani S，Sevanan M，Krishnamoorthy A，et al. A systematic review of molecular approaches that link mitochondrial dysfunction and neuroinflammation in Parkinson’s disease ［J］. Neurol Sci，2021，42（11）：4459-4469.

［3］Spampinato SF，Merlo S，Sano Y，et al. Astrocytes contribute to Aβ-induced blood-brain barrier damage through activation of endothelial MMP9 ［J］. J Neurochem，2017，142（3）：464-477.

［4］Li YF，Nanayakkara G，Sun Y，et al. Analyses of caspase-1-regulated transcriptomes in various tissues lead to identification of novel IL-1β，IL-18 and sirtuin-1 independent pathways ［J］. J Hematol Oncol，2017，10（1）：40.

［5］Duan H，Li L，Shen S，et al.Hydrogen sulfide reduces cognitive impairment in rats after subarachnoid hemorrhage by ameliorating neuroinflammation mediated by the TLR4/NF-κB pathway in microglia ［J］. Front Cell Neurosci，2020，14：210.

［6］Tabassum R，Jeong NY，Jung J. Therapeutic importance of hydrogen sulfide in age-associated neurodegenerative diseases ［J］. Neural Regen Res，2020，15（4）：653-662.

［7］Lama J，Buhidma Y，Fletcher EJR，et al. Animal models of Parkinson’s disease: a guide to selecting the optimal model for your research ［J］. Neuronal Signal，2021，5（4）：Ns20210026.

［8］Lin Zh，Chen HZh，Zhao H，et al. Preparation and assessment of a C57BL/6 mouse Parkinson’s model induced by MPTP ［J］. Chinese Journal of Comparative Medicine，2020，30（8）：57-62,85.（in Chinese）

林臻，陈洪志，赵航，等. MPTP诱导C57BL/6小鼠帕金森模型的制备和评估［J］. 中国比较医学杂志，2020，30（8）：57-62, 85.

［9］Huang Z，Zhou T，Sun X，et al. Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation ［J］. Cell Death Differ，2018，25（1）：180-189.

［10］Liu YT, Sun MH, Cai ChW，et al. Research progress on neural mechanism of peripheral inflammation in Parkinson’s disease ［J］. Journal of Physiology，2019，71（5）：732-740.（in Chinese）

刘泳廷，孙铭浩，蔡春伟，等. 外周炎症促发帕金森病的神经机制研究进展［J］. 生理学报，2019，71（5）:732-740.

［11］Xiao XY, Pei Y. Research progress on pathogenesis of glial cells and inflammatory factors associated with inflammation of Parkinson’s disease ［J］. Liaoning Journal of Traditional Chinese Medicine，2018，45（11）：2451-2454.（in Chinese）

肖潇雨，裴媛胶质细胞及炎症因子与帕金森病炎症发病机制的研究进展［J］. 辽宁中医杂志，2018，45（11）：2451-2454.

［12］Yamaguchi T，Miyamoto T，Shikata E，et al. Activation of the NLRP3/IL-1β/MMP-9 pathway and intracranial aneurysm rupture associated with the depletion of ERα and Sirt1 in oophorectomized rats ［J］. J Neurosurg，2022，138(1):191-198.

［13］Wang HB，Yu WR. Advances in the research of MMP-2/MMP-9 in inflammation ［J］. Medical Review, 2014, 20（17）: 3120-3122.（in Chinese）

王海波，俞为荣. MMP-2/MMP-9在炎症中的研究进展［J］. 医学综述，2014，20（17）：3120-3122.

［14］Guo P，Liu L，Yang X，et al. Irisin improves BBB dysfunction in SAP rats by inhibiting MMP-9 via the ERK/NF-κB signaling pathway ［J］. Cell Signal，2022，93：110300.

［15］Ruan Z，Zhang D，Huang R，et al. Microglial activation damages dopaminergic neurons through MMP-2/-9-mediated increase of blood-brain barrier permeability in a Parkinson’s disease mouse model ［J］. Int J Mol Sci，2022，23（5）：2793.

［16］Zhang C，Zhao M，Wang B，et al. The Nrf2-NLRP3-Caspase-1 axis mediates the neuroprotective effects of celastrol in Parkinson’s disease ［J］. Redox Biol，2021，47：102134.

［17］Salvatore MF, Mcinnis TR, Cantu MA，et al. Tyrosine hydroxylase inhibition in substantia nigra decreases movement frequency ［J］. Mol Neurobiol，2019，56（4）：2728-2740.

［18］Liu L，Luo GX，Lin JL，et al. Effects of cordycepin on motor and cognition in Parkinson disease mice induced by MPTP ［J］. Chinese Journal of Pathophysiology，2019，35（2）：326-331.（in Chinese）

刘丽，罗广轩，林健琳，等. 虫草素对 MPTP 诱导的帕金森病小鼠运动与认知能力的影响［J］.中国病理生理杂志，2019，35（2）：326-331.

［19］Liu JF，Chen ShSh，Feng W，et al. Hydrogen sulfide inhibits the M1 polarization of microglia induced by lipopolysaccharide the JAK2/STAT3 pathway ［J］. Chinese Journal of Neuroimmunology and Neurology，2020，27（3）：184-194（in Chinese）

刘剑锋，陈杉杉，冯伟，等. 硫化氢通过JAK2/STAT3通路抑制脂多糖诱导的小胶质细胞M1型极化［J］. 中国神经免疫学和神经病学杂志，2020，27（3）：184-194.

［20］Paul BD，Snyder SH. Gasotransmitter hydrogen sulfide signaling in neuronal health and disease ［J］. Biochem Pharmacol，2018，149：101-109.

［21］Hu LF，Lu M，Tiong CX，et al. Neuroprotective effects of hydrogen sulfide on Parkinsons disease rat model ［J］. Aging Cell, 2010，9 （2）：135-146.

［22］Ghanbari F，Khaksari M，Vaezi G，et al. Hydrogen sulfide protects hippocampal neurons against methamphetamine neurotoxicity via inhibition of apoptosis and neuroinflammation ［J］. J Mol Neurosci，2019，67（1）：133-141.

［23］Kumar M, Sandhir R. Hydrogen sulfide suppresses homocysteine-induced glial activation and inflammatory response ［J］. Nitric Oxide，2019，90：15-28.

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