金丝桃苷抑制帕金森病小鼠小胶质细胞NLRP3表达缓解DA能神经元损伤的研究

Hypericin inhibits the expression of NLRP3 in microglia of Parkinson's disease mice and alleviates the damage of DA-ergic neurons

范丽珊 ¹张佳 ¹牛思翔 ¹肖琪 ¹樊慧杰 ¹徐磊 ¹杨丽霞 ¹贾璐 ¹秦劭晨 ²肖保国 ³马存根 ¹柴智¹

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作者信息

1. 山西中医药大学多发性硬化益气活血重点研究室/神经生物学研究中心,山西晋中 030619
2. 山西中医药大学第一临床学院神经内科,山西太原 030024
3. 复旦大学华山医院神经病学研究所,上海 200025
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摘要

目的观察金丝桃苷(HYP)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠模型的干预作用,及其作用机制.方法将30只C57BL/6小鼠随机分为正常组、模型组和实验组,每组10只.MPTP腹腔注射7 d后,建立PD小鼠模型,造模的第1天起进行药物干预.正常组和模型组均腹腔注射500 µL·kg·d-1 0.9％NaCl;实验组腹腔注射25 mg·kg·d-1 HYP.3组小鼠每天给药1次,持续14 d.观察小鼠的行为学表现,用蛋白质印迹法检测小鼠黑质纹状体酪氨酸羟化酶(TH)、Nod样受体热蛋白结构域蛋白3(NLRP3)和离子钙结合衔接分子(Iba1)蛋白的表达水平.结果正常组、模型组和实验组的爬杆时间分别为(5.35±0.43)、(9.71±1.19)和(8.07±0.34)s,悬挂得分分别为(2.92±0.15)、(1.38±0.28)和(1.96±0.28)分,TH蛋白相对表达水平分别为1.04±0.06、0.51±0.09和0.75±0.07,NLRP3蛋白相对表达水平分别为0.51±0.03、1.00±0.04和0.77±0.06,Iba1蛋白相对表达水平分别为0.68±0.10、1.30±0.28和0.89±0.05.模型组的上述指标与实验组和正常组比较,在统计学上差异均有统计学意义(均P＜0.01).结论 HYP通过抑制PD小鼠脑中NLRP3炎症小体的表达来发挥对PD的治疗作用.

Abstract

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

关键词

金丝桃苷/帕金森病/Nod样受体热蛋白结构域蛋白3

Key words

hyperoside/Parkinson's disease/Nod-like receptor heat protein domain protein 3

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基金项目

国家中医药管理局青年岐黄学者培养基金资助项目(国中医药人教函[2022]256号)

山西省重点国别科技合作基金资助项目(202204041101002)

山西省青年拔尖人才支持计划基金资助项目(晋组办字[2019]35号)

山西省省筹资金资助回国留学人员科研基金资助项目(2021-142)

山西省"四个一批"科技兴医创新计划医学科技领军人才基金资助项目(2020RC05)

山西省晋中市科技重点研发计划(社会发展)基金资助项目(Y213004)

山西省卫健委科研课题基金资助项目(2023084)

山西省中医药科研课题基金资助项目(2022ZYYC091)

山西中医药大学创新能力培育计划基金资助项目(2021PY-QN-03)

山西中医药大学创新能力培育计划基金资助项目(2022TD1013)

山西省研究生教育创新基金资助项目(2022Y714)

山西省研究生科研实践类基金资助项目(2023KY669)

山西中医药大学研究生教育创新计划基金资助项目(2023CX001)

出版年

2024

中国临床药理学杂志

中国药学会

中国临床药理学杂志

CSTPCDCSCD北大核心

影响因子：1.91

ISSN：1001-6821

参考文献量17

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