目的 探索Nrf2/HO-1通路是否参与远志皂苷元（远志）在脑出血体外细胞模型中对BV2小胶质细胞炎症反应的调控作用。方法 采用红细胞与BV2小鼠小胶质细胞共培养构建体外脑出血模型。分别给予远志单独处理、远志联合Nrf2抑制剂ML385处理，检测炎症因子水平。收集细胞上清制备条件培养基，用于培养SH-SY5Y人神经母细胞瘤细胞，并检测其铁死亡水平。结果 模型组BV2细胞炎症因子（IL-1β，IL-6，TNF-α）水平较对照组显著升高（P＜0.001）；高浓度远志（20 μM）可降低炎症因子水平，并上调Nrf2/HO-1通路蛋白表达，而ML385能逆转该作用。模型组条件培养基可诱导SH-SY5Y细胞铁死亡，而经远志处理的BV2细胞条件培养基则减轻该现象；ML385预处理可削弱远志对SH-SY5Y细胞的保护作用，远志组铁离子、丙二醛、转铁蛋白受体1水平低于远志联合ML385组（P＜0.05），铁转运蛋白、谷胱甘肽和谷胱甘肽过氧化物酶水平高于远志联合ML385组（P＜0.05）。结论 远志皂苷元通过激活Nrf2/HO-1通路抑制BV2小胶质细胞炎症反应，并在脑出血体外模型中发挥神经保护作用。

     Objective To investigate whether the Nrf2/HO1 signaling pathway is involved in the regulatory effect of tenuigenin（TEN）on the inflammatory response of BV2 microglial cells in an in vitro intracerebral hemorrhage（ICH）model．Methods An in vitro ICH model was established by coculturing BV2 murine microglial cells with red blood cells．Cells were treated with TEN alone or in combination with the Nrf2 inhibitor ML385，and the levels of inflammatory factors were measured．The conditioned medium collected from the cell supernatant was used to culture SHSY5Y human neuroblastoma cells，and ferroptosis levels were assessed．Results The levels of inflammatory factors（IL-1β，IL-6，TNF-α）in BV2 cells of the model group were significantly higher than those in the control group（P＜0.001）．High concentration of TEN（20 μM）could reduce the levels of inflammatory factors and up-regulate the expression of Nrf2/HO-1 pathway proteins，while ML385 could reverse this effect．The conditioned medium of the model group could induce ferroptosis in SH-SY5Y cells，while the conditioned medium of BV2 cells treated with TEN could alleviate this phenomenon．Pretreatment with ML385 could weaken the protective effect of TEN on SH-SY5Y cells．The levels of iron ions，malondialdehyde and transferrin receptor protein 1 in the TEN group were lower than those in the TEN combined with ML385 group（P＜0.05），while the levels of ferroportin glutathione and glutathione peroxidase 4 were higher than those in the TEN combined with ML385 group（P＜0.05）．Conclusions TEN inhibits the inflammatory response of BV2 microglial cells by activating the Nrf2/HO1 pathway and exerts a neuroprotective effect in the in vitro ICH model．

帕金森病（PD）是一种常见的与年龄相关的神经退行性疾病,其特点是黑质致密部内多巴胺能神经元的进行性丢失以及路易小体的积累。多巴胺能神经元的退化导致纹状体的多巴胺水平降低,最终出现静息性震颤、运动迟缓、肌肉僵硬和姿势不稳等运动症状,以及认知能力下降、嗅觉功能受损、精神异常和睡眠障碍等非运动症状。由于人口结构转变和全球老龄化,PD的不断增加对患者、家庭和社会构成重大负担。尽管广泛的研究已阐明了PD的病因学和潜在机制,但现有治疗主要集中在症状管理,无法阻止疾病的进展。小胶质细胞作为脑内重要的免疫细胞,对维持中枢神经系统的稳态具有关键作用。本文综述了PD研究,包括其病因学因素、分子机制和现有治疗策略。此外,审视了在PD样模型中涉及小胶质细胞的研究,深入探讨了小胶质细胞在疾病进展中的动态,并探究了小胶质细胞在促进或减轻疾病进展方面所扮演的错综角色。通过这样的探讨,本综述旨在为PD复杂的发病机制提供新的洞见和观点,激发出针对性治疗干预的创新思路。

Parkinson's disease（PD）,a prevalent age-related neurodegenerative disorder,is characterized by the progressive loss of dopaminergic neurons within the substantia nigra compacta（SNc）and the accumulation of Lewy bodies．The degeneration of dopaminergic neurons leads to diminished striatal dopamine levels,culminating in motor symptoms such as resting tremors,bradykinesia,muscle rigidity and postural instability,alongside non-motor manifestations encompassing cognitive decline,impaired olfactory function,psychological abnormalities and sleep disturbances．The escalating incidence of PD due to shifting demographics and global aging poses substantial burdens on patients,families and society．Although extensive research has elucidated the etiology and underlying mechanisms of PD,available treatments largely focus on symptom management and lack the capacity to halt disease progression．Microglia,as integral immune cells within the brain,wield pivotal influence over central nervous system homeostasis．This review presents a comprehensive synthesis of PD,encompassing its etiological factors,molecular mechanisms,and existing therapeutic strategies．Furthermore,we scrutinized research involving microglia in PD-like models,delving into the dynamics of microglia in disease progression and probing into the intricate roles that microglia assume in either fostering or mitigating disease advancement．By doing so,this review aims to furnish novel insights and perspectives that shed light on the intricate pathogenesis of PD,potentially sparking innovative concepts for targeted therapeutic interventions．