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癫痫清颗粒含药血清抑制小胶质细胞铁死亡的机制研究
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| 篇名： | 癫痫清颗粒含药血清抑制小胶质细胞铁死亡的机制研究 |
| TITLE： | Mechanism of drug-containing serum of Dianxianqing granules in inhibiting microglial ferroptosis |
| 摘要： | 目的 探究癫痫清颗粒含药血清（DXQ）抑制小胶质细胞铁死亡的潜在机制。方法取雄性SD大鼠，分别以生理盐水和癫痫清颗粒药液灌胃，制备正常血清和DXQ。取小鼠小胶质细胞BV2，将成功转染阴性对照小干扰RNA（si-NC）的细胞设为si-NC组，正常培养；将成功转染谷胱甘肽过氧化物酶4（GPX4）小干扰RNA（si-GPX4）的细胞分为si-GPX4组、CsA组（1μmol/L环孢素A）和DXQ-L、DXQ-M、DXQ-H组（5%、7%、10%DXQ），分别以相应药液和铁死亡诱导剂Erastin（10μmol/L）干预。培养48h后，检测各组细胞中总铁离子、谷胱甘肽（GSH）含量，活性氧（ROS）及线粒体内超氧化物的表达水平，线粒体膜电位及线粒体通透性转换孔（MPTP）开放情况，GPX4、亲环蛋白D（CypD）mRNA的表达情况，以及铁死亡相关蛋白[GPX4、转铁蛋白受体1（TfR1）、铁蛋白重链1（FTH1）]、MPTP相关蛋白[腺苷酸转运蛋白（ANT）、细胞色素C（CytC）、线粒体钙单向转运体（MCU）、CypD]的表达情况。结果与si-NC组相比，si-GPX4组细胞中总铁离子含量、ROS及线粒体内超氧化物表达水平、MPTP开放程度、CypD蛋白及其mRNA以及TfR1、MCU蛋白的表达均显著升高或上调（P＜0.01），GSH含量、线粒体膜电位、GPX4蛋白及其mRNA以及FTH1、ANT、CytC蛋白的表达均显著降低或下调（P＜0.01）；与si-GPX4组相比，DXQ-M、DXQ-H组细胞上述定量指标均普遍改善（P＜0.01或P＜0.05）。结论DXQ可通过激活GSH/GPX4通路以增强细胞抗氧化能力，调控TfR1、FTH1蛋白表达以纠正铁离子稳态，抑制MPTP过度开放以改善线粒体功能，最终抑制小胶质细胞铁死亡。 |
| ABSTRACT： | OBJECTIVE To explore the potential mechanism by which drug-containing serum of Dianxianqing granules （DXQ） inhibits microglial ferroptosis. METHODS Male SD rats were given normal saline and Dianxianqing granules solution via intragastric administration to prepare normal serum and DXQ， respectively. Mice microglia BV2 cells were collected and successfully transfected with a negative control small interfering RNA （si-NC）， and then they were included in the si-NC group and cultured under normal conditions. Cells successfully transfected with small interfering RNA targeting glutathione peroxidase 4 （GPX4） （si-GPX4） were divided into the si-GPX4 group， the CsA group （treated with 1 μmol/L cyclosporine A）， and the DXQ- L， DXQ-M and DXQ-H groups （treated with 5%， 7% and 10% DXQ， respectively）. These groups were subsequently treated with their corresponding drug solutions and ferroptosis inducer Erastin （10 μmol/L）. The intracellular levels of total iron ions， glutathione （GSH）， reactive oxygen species （ROS）， and the expression of mitochondrial superoxide were determined in each group after 48 h of treatment. Additionally， mitochondrial membrane potential， the opening degree of mitochondrial permeability transition pore （MPTP）， and mRNA expressions of GPX4 and cyclophilin D （CypD） were detected. Furthermore， the expressions of ferroptosis-related proteins[GPX4， transferrin receptor 1 （TfR1） and ferritin heavy chain 1 （FTH1）]， as well as MPTP-related proteins [adenine nucleotide translocator （ANT）， cytochrome C （CytC）， mitochondrial calcium uniporter （MCU） and CypD] were assessed. RESULTS Compared with si-NC group， the levels of total iron ions and ROS， the expression level of mitochondrial superoxide， the opening degree of MPTP， protein and its mRNA expressions of CypD as well as protein expressions of TfR1 and MCU were increased or up-regulated significantly （P＜0.01）； however， GSH content， mitochondrial membrane potential， protein and mRNA expressions of GPX4， and protein expressions of FTH1， ANT and CytC were decreased or down-regulated significantly （P＜0.01）. Compared with the si-GPX4 group， the cells in the DXQ-M， DXQ-H groups showed a general improvement in the above quantitative indicators （P＜0.01 or P＜0.05）. CONCLUSIONS DXQ can enhance antioxidant capacity by activating the GSH/GPX4 pathway， regulate the expressions of TfR1 and FTH1 protein to correct iron ion homeostasis， inhibit excessive opening of MPTP to improve mitochondrial function， and ultimately suppress microglial ferroptosis. |
| 期刊： | 2026年第37卷第03期 |
| 作者： | 范广坤；齐越；王籍贤；陈巍；夏春鹏；王一行；赵玥；安阳 |
| AUTHORS： | FAN Guangkun，QI Yue，WANG Jixian，CHEN Wei，XIA Chunpeng，WANG Yihang，ZHAO Yue，AN Yang |
| 关键字： | 癫痫清颗粒；线粒体通透性转换孔；GSH/GPX4通路；铁死亡；小胶质细胞 |
| KEYWORDS： | Dianxianqing granules； mitochondrial permeability transition pore； GSH/GPX4 pathway； ferroptosis； microglia |
| 阅读数： | 3 次 |
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