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作 者:张培根 朱海丽 高卉[1] ZHANG Pei-gen;ZHU Hai-li;GAO Hui(School of Pharmacy,Hubei University of Science and Technology,Xianning Hubei 437100,China)
机构地区:[1]湖北科技学院医学部药学院,湖北咸宁437100
出 处:《中国药理学通报》2025年第1期94-100,共7页Chinese Pharmacological Bulletin
基 金:湖北省自然科学基金资助项目(No 2023AFB1087)。
摘 要:目的探究人参皂苷Rg3在慢性神经性疼痛中的作用及机制。方法筛选并分析慢性神经性疼痛数据中前额叶皮层内差异性表达基因;小鼠随机分为假手术组、模型组及给药组;采用坐骨神经慢性压迫损伤模型构建神经病理性疼痛动物模型,腹腔注射人参皂苷Rg3给药;记录小鼠痛觉行为变化;HE染色、尼氏染色、免疫印迹及免疫组化检测各组PFC脑组织神经和线粒体损伤情况;分子对接探究人参皂苷Rg3的作用靶点;Mito-Tracker检测线粒体膜电位;ATP试剂盒分析ATP含量。结果与假手术组相比,模型组小鼠表现为痛觉过敏和运动能力受损;PFC内神经及线粒体损伤(P<0.05)。与模型组相比,人参皂苷Rg3给药可增加小鼠机械痛阈值、热缩足潜伏期和转棒停留时间;同时降低PFC内炎性细胞、尼氏小体及Dnm1l阳性细胞数,下调c-Fos、IL-1β和Dnm1l蛋白表达水平(P<0.05)。分子对接显示人参皂苷Rg3可结合Dnm1l。在细胞水平,人参皂苷Rg3给药可升高线粒体膜电位和ATP含量(P<0.05)。结论人参皂苷Rg3可通过调控降低PFC内炎症因子和线粒相关蛋白表达,改善线粒体功能,缓解CCI小鼠痛觉过敏。Aim To explore the role and mechanism of ginsenoside Rg3 in chronic neuropathic pain.Methods The differentially expressed genes in the prefrontal cortex of chronic neuropathic pain were screened and analyzed.The mice were randomly divided into the sham operation group,model group and drug administration group.Neuropathic pain animal model was established by chronic sciatic nerve compression injury model.Ginsenoside Rg3 was injected intraperitoneally.The changes of pain behavior in mice were recorded.HE staining,Nissl staining,Western blot and immunohistochemistry were used to detect nerve and mitochondrial damage in PFC brain tissue of each group.Molecular docking was used to explore the target of ginsenoside Rg3.Mito-Tracker was used to detect mitochondrial membrane potential,and ATP kit was employed to analyze ATP content.Results Compared with the sham operation group,mice in the model group showed hyperalgesia and impaired motor ability,and nerve and mitochondrial damage in PFC(P<0.05).Compared with the model group,ginsenoside Rg3 administration could increase the mechanical pain threshold,thermal foot contraction latency and stick rotation residence time of mice.At the same time,the number of inflammatory cells,Nishi bodies and Dnm1l positive cells in PFC decreased,and the expression levels of c-Fos,IL-1βand Dnm1l protein were down-regulated(P<0.05).Molecular docking showed that ginsenoside Rg3 could bind Dnm1l.At the cellular level,ginsenoside Rg3 administration increased mitochondrial membrane potential and ATP content(P<0.05).Conclusion Ginsenoside Rg3 can reduce the expression of inflammatory factors and mitochondria-related proteins in PFC,improve mitochondrial function,and relieve pain hypersensitivity in CCI mice.
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