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．

       目的   探讨谷氨酸对HT22细胞线粒体自噬和细胞凋亡的影响，并评估虾青素预处理的保护作用及其分子机制。方法   用谷氨酸及虾青素处理HT22细胞，通过蛋白印迹及聚合酶联反应等评估其对线粒体自噬的影响。结果   谷氨酸处理显著抑制线粒体初级自噬（PINK1、Parkin、pULK1^ser555和LC3Ⅱ）和次级自噬（LAMP1和Rab7），上调cleaved Caspase-3的表达（P＜0.05）。虾青素预处理减少细胞凋亡，恢复了线粒体自噬，PINK1、Parkin、pULK1^ser555和LC3Ⅱ的表达水平上升（分别为2.3倍、2.6倍、83.3%及81.1%）（P＜0.05），该作用被自噬抑制剂BafA1阻断。此外，谷氨酸抑制Nrf2核内转移和NLRX1表达，而预处理显著促进Nrf2的核内转移并上调NLRX1，分别上调25.8%、33.2%。生物信息学分析显示NLRX1启动子区域含有3个Nrf2结合位点，提示Nrf2通过调控NLRX1转录活性发挥作用。结论   文章揭示虾青素通过Nrf2/NLRX1通路激活线粒体自噬，展现神经保护作用。

       Objective  To explore the effects of glutamate on mitophagy and apoptosis in HT22 cells and evaluate the protective effects and molecular mechanisms of astaxanthin pretreatment．Methods  HT22 cells were treated with glutamate and astaxanthin．The effects on mitophagy were assessed using Western Blot and PCR．Results  Glutamate treatment  significantly inhibited primary mitophagy（PINK1，Parkin，pULK1^ser555 and LC3II）and secondary mitophagy（LAMP1 and Rab7）while upregulating cleaved Caspase-3 expression．Astaxanthin pretreatment notably reduced apoptosis and restored mitophagy，the expression levels of PINK1，Parkin，pULK1^ser555 and LC3II were significantly upregulated（by 2.3-fold，2.6-fold，83.3% and 81.1% respectively，P＜0.05），but this effect was blocked by the autophagy inhibitor BafA1．Additionally，glutamate suppressed Nrf2 nuclear translocation and NLRX1 expression，whereas astaxanthin promoted Nrf2 nuclear translocation and increased NLRX1 expression by 25.8% and 33.2%，respectively．Bioinformatics analysis  revealed three Nrf2 binding sites in the NLRX1 promoter region，suggesting that Nrf2 may regulate NLRX1 transcriptional activity．Conclusions  The study demonstrates that astaxanthin exhibited potential neuroprotective effect by activating mitophagy through the Nrf2/NLRX1 pathway．