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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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          范广坤 ,齐 越 ,王籍贤 ,陈 巍 ,夏春鹏 ,王一行 ,赵 玥 ,安 阳(1. 辽宁中医药大学药学院,辽宁
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          大连 116600;2.徐州医药高等职业学校药学技术系,江苏 徐州 221116;3.辽宁中医药大学附属第二医院
          中药药学室,沈阳 110034;4.辽宁中医药大学研究生院,沈阳 110847)
          中图分类号  R965;R285      文献标志码  A      文章编号  1001-0408(2026)03-0317-07
          DOI  10.6039/j.issn.1001-0408.2026.03.08
          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(1 μmol/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(10 μmol/L)干预。培养 48 h
          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。
          关键词  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

          Mechanism of drug-containing serum of Dianxianqing granules in inhibiting microglial ferroptosis
          FAN Guangkun ,QI Yue ,WANG Jixian ,CHEN Wei ,XIA Chunpeng ,WANG Yihang ,ZHAO Yue ,AN Yang         4
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         (1. College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Liaoning Dalian 116600, China;
          2.  Dept.  of  Pharmaceutical  Technology,  Xuzhou  Medical  Higher  Vocational  School,  Jiangsu  Xuzhou  221116,
          China;3. Dept. of Traditional Chinese Medicine Pharmacy, Second Affiliated Hospital of Liaoning University of
          Traditional Chinese Medicine, Shenyang 110034, China;4. Graduate School, Liaoning University of Traditional
          Chinese Medicine, Shenyang 110847, China)
          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
             Δ 基金项目 国家自然科学基金面上项目(No.82575043);辽宁省           (TfR1) and ferritin heavy chain 1 (FTH1)], as well as MPTP-
          博士科研启动基金计划项目(No.2025-BS-0702)                      related  proteins  [adenine  nucleotide  translocator  (ANT),
             *第一作者 硕士研究生。研究方向:神经药理学。E-mail:
                                                             cytochrome  C  (CytC) ,  mitochondrial  calcium  uniporter
          17320070590@163.com
             # 通信作者 研究员,硕士生导师,博士。研究方向:中药制剂药效                (MCU)  and  CypD]  were  assessed.  RESULTS  Compared  with
          物质基础及质量控制。E-mail:z.yue2008@163.com                 si-NC  group,  the  levels  of  total  iron  ions  and  ROS,  the


          中国药房  2026年第37卷第3期                                                 China Pharmacy  2026 Vol. 37  No. 3    · 317 ·
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