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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 ·

