外源性H2S对帕金森病模型小鼠神经保护作用及其对基质金属蛋白酶9和Caspase-1表达的影响

doi:10.16098/j.issn.0529-1356.2023.03.006

解剖学报 ›› 2023, Vol. 54 ›› Issue (3): 289-295.doi: 10.16098/j.issn.0529-1356.2023.03.006

外源性H2S对帕金森病模型小鼠神经保护作用及其对基质金属蛋白酶9和Caspase-1表达的影响

刘柯婷¹ 陈缤彬²税玉莲³ 石清明⁴肖莉^5*

1.成都市第七人民医院神经内科，成都610200; 2.成都医学院2019 级麻醉学专业，成都610500; 3.成都医学院2020级麻醉学专业，成都610500; 4.西部战区疾病预防控制中心，兰州730020; 5.成都医学院人体解剖学教研室/发育与再生重点实验室，成都610500

收稿日期:2022-09-30 修回日期:2022-11-22 出版日期:2023-06-06 发布日期:2023-06-06
通讯作者: 肖莉 E-mail:18692990@qq.com
基金资助:
成都市卫健委科研课题;成都医学院—成都市第七人民医院联合科研基金项目

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*

1.Department of Neurology，Chengdu Seventh People’s Hospital, Chengdu 610200,China; 2.Grade 2019 of Anesthesiology，Chengdu Medical College, Chengdu 610500,China; 3.Grade 2020 of Anesthesiology，Chengdu Medical College, Chengdu610500,China; 4.Center of Disease Control and Prevention，Western Theater Command, Lanzhou 730020,China; 5.Department of Human Anatomy，Chengdu Medical College/Key Laboratory of Development and Regeneration, Chengdu 610500,China

Received:2022-09-30 Revised:2022-11-22 Online:2023-06-06 Published:2023-06-06
Contact: XIAO Li E-mail:18692990@qq.com

摘要/Abstract

摘要：

目的探讨外源性硫化氢（H2S）对1-甲基-4-苯基-1, 2, 3, 6-四氢吡啶（MPTP）对诱导的帕金森病（PD）小鼠保护作用及其对基质金属蛋白酶9(MMP-9)和Caspase-1表达的影响。方法将36只雄性昆明小鼠随机分为对照组（control）、PD组和PD+硫氢化钠（NaHS）组，每组12只。腹腔注射MPTP（30 mg/kg），每天1次，连续7 d诱导PD小鼠模型，PD+NaHS组于模型制作前30 min腹腔注射5.6 mg/kg NaHS（H2S供体），对照组给予等量生理盐水。采用震颤麻痹评分、悬挂实验评估小鼠行为学变化，HE染色观察各组小鼠中脑黑质（SN）神经元的形态学改变；免疫组织化学和Western blotting法检测各组中脑SN区酪氨酸羟化酶（TH）、MMP-9和Caspase-1蛋白表达。结果与control组比较，PD组小鼠震颤麻痹评分增高（P＜0.05），悬挂实验评分降低（P＜0.05）；光学显微镜下中脑SN区神经元数量明显减少，排列紊乱，部分神经元胞体固缩，胞质红染；SN区TH阳性细胞数及TH蛋白表达降低（P＜0.05），MMP-9与Caspase-1阳性细胞数及MMP-9与Caspase-1蛋白表达水平增加（P＜0.05）。与PD组相比，PD+NaHS组小鼠震颤麻痹评分降低（P＜0.05），悬挂实验评分增加（P＜0.05），SN区神经元数量明显增多；SN区TH阳性细胞数及TH蛋白表达水平增加（P＜0.05），MMP-9与Caspase-1阳性细胞数及MMP-9与Caspase-1蛋白表达水平降低（P<0.05）。结论外源性H2S对PD小鼠黑质多巴胺能神经元具有保护作用，其机制可能与抑制MMP-9与Caspase-1介导的神经炎症反应有关。

关键词: 硫化氢, 帕金森病, 基质金属蛋白酶9, 半胱氨酸的天冬氨酸蛋白水解酶1, 免疫组织化学, 免疫印迹法, 小鼠

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

中图分类号:

R364.5

刘柯婷陈缤彬税玉莲石清明肖莉. 外源性H2S对帕金森病模型小鼠神经保护作用及其对基质金属蛋白酶9和Caspase-1表达的影响[J]. 解剖学报, 2023, 54(3): 289-295.

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.

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外源性H2S对帕金森病模型小鼠神经保护作用及其对基质金属蛋白酶9和Caspase-1表达的影响

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

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