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

LIU Ke-Ting; CHEN Bin-Bin; SHUI Yu-Lian; SHI Qing-Ming; XIAO Li

doi:10.16098/j.issn.0529-1356.2023.03.006

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Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (3) : 289-295. DOI: 10.16098/j.issn.0529-1356.2023.03.006

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

LIU Ke-ting¹ CHEN Bin-bin² SHUI Yu-lian³ SHI Qing-ming⁴ XIAO Li^5*

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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

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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 https://doi.org/10.16098/j.issn.0529-1356.2023.03.006

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