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人参皂苷Rd通过下调DRP1介导的线粒体分裂缓解哮喘

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目的:探讨人参皂苷Rd通过发动蛋白相关蛋白1(DRP1)介导的线粒体分裂缓解蟑螂提取物(CRE)诱导的哮喘小鼠气道炎症的分子机制.方法:动物(BALB/c小鼠)和细胞(人气道上皮BEAS-2B细胞)实验均设置对照组、模型组(CRE组)、CRE+低剂量人参皂苷Rd组、CRE+高剂量人参皂苷Rd组和CRE+地塞米松组.利用HE染色法观察肺组织病理改变;ELISA及流式细胞术检测辅助性T细胞(Th1/Th2)因子水平;Western blot和荧光染色法检测活性氧(ROS)产生、线粒体分裂蛋白及线粒体形态.结果:人参皂苷Rd显著减轻CRE诱导的小鼠气道周围炎症细胞浸润,降低血清总免疫球蛋白E(IgE)和CRE特异性IgE水平(P<0.05),以及支气管肺泡灌洗液中嗜酸性粒细胞比例(P<0.05),纠正Th1/Th2失衡(P<0.05).人参皂苷Rd还可降低模型小鼠肺组织和CRE诱导的BEAS-2B细胞中DRP1、p-DRP1(Ser616)和线粒体分裂蛋白1(FIS1)水平(P<0.05),改善线粒体形态,抑制ROS产生.结论:人参皂苷Rd通过下调DRP1介导的线粒体分裂,减轻CRE诱导的哮喘气道炎症.本研究对人参皂苷Rd在哮喘模型中的免疫药理作用提出了新的见解.
Mechanism of ginsenoside Rd in alleviating asthma by down-regulating DRP1-mediated mitochondrial fission
AIM:To explore the molecular mechanism by which ginsenoside Rd alleviates airway inflamma-tion induced by cockroach extract(CRE)in asthmatic mice through dynamin-related protein 1(DRP1)-mediated mito-chondrial fission.METHODS:BALB/c mice and human airway epithelial BEAS-2B cells were divided into control group,model group(CRE group),CRE+low-dose ginsenoside Rd group,CRE+high-dose ginsenoside Rd group,and CRE+dexamethasone group.The pathological changes of lung tissues were observed by HE staining.The levels of helper T cell(Th1/Th2)factors were detected by ELISA and flow cytometry.Western blot and fluorescence staining were used to detect reactive oxygen species(ROS)production,mitochondrial fission proteins,and mitochondrial morphology.RE-SULTS:Ginsenoside Rd significantly attenuated CRE-induced inflammatory cell infiltration around the airway,reduced serum total immunoglobulin E(IgE)and CRE-specific IgE levels(P<0.05),decreased the proportion of eosinophils in bronchoalveolar lavage fluid(P<0.05),and corrected the imbalance of Th1/Th2(P<0.05).Ginsenoside Rd also reduced the levels of DRP1,p-DRP1(Ser616)and mitochondrial fission protein 1(FIS1)in the lung tissue of model mice and BE-AS-2B cells induced by CRE(P<0.05),improved mitochondrial morphology,and inhibited ROS production.CONCLU-SION:Ginsenoside Rd attenuates CRE-induced asthma airway inflammation by down-regulating DRP1-mediated mito-chondrial fission.Our findings provide new insights into the immunopharmacological effects of ginsenoside Rd in asthma models.

ginsenoside Rddynamin-related protein 1mitochondriaasthma

李祎、马立光

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延边大学医学院,吉林 延吉 133002

延边大学医学院口腔教研室,吉林 延吉 133002

人参皂苷Rd 发动蛋白相关蛋白1 线粒体 哮喘

吉林省自然科学基金资助项目

YDZJ202201ZYTS140

2024

中国病理生理杂志
中国病理生理学会

中国病理生理杂志

CSTPCD北大核心
影响因子:1.065
ISSN:1000-4718
年,卷(期):2024.40(7)
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