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心脑舒通胶囊抑制铁死亡减轻大鼠脑缺血再灌注损伤的机制
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          李华妮    1, 2* ,刘长河  1, 2 # ,郭晓燕 ,钟 鑫 ,张 薇 ,葛文静 (1.河南省中西医结合医院中药研究所,郑州
          450004;2.河南省中药制剂工程技术研究中心,郑州 450004;3.郑州卷烟厂康复医院药剂科,郑州 450047)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2025)03-0306-06
          DOI  10.6039/j.issn.1001-0408.2025.03.08

          摘   要  目的  研究心脑舒通胶囊调控铁死亡途径减轻大鼠脑缺血再灌注损伤(CIRI)的机制。方法  将大鼠随机分为假手术组,
          模型组,心脑舒通低、高剂量组(220、440 mg/kg),银杏叶提取物组(阳性对照,150 mg/kg)。各组大鼠灌胃相应药液/生理盐水,连
          续7 d。采用短暂性大脑中动脉闭塞法复制CIRI模型,术后24 h进行取材,检测大鼠脑梗死面积,并计算脑梗死率;观察大鼠脑组
          织病理学变化;检测大鼠脑组织中总铁和血清中脂质过氧化物(LPO)、丙二醛(MDA) 、谷胱甘肽(GSH)水平;检测大鼠脑组织中
          核转录因子红系2相关因子2(Nrf2)/血红素氧合酶1(HO-1)/谷胱甘肽过氧化物酶4(GPX4)蛋白和mRNA表达水平。结果  与模
          型组比较,银杏叶提取物组和心脑舒通各剂量组大鼠脑梗死率、脑组织中总铁水平、血清中LPO水平(银杏叶提取物组和心脑舒
          通低剂量组除外)均显著降低(P<0.05或P<0.01);血清中GSH水平以及脑组织中Nrf2、HO-1、GPX4蛋白和mRNA表达水平均
          显著升高(P<0.05或P<0.01);脑组织病理损伤减轻,神经细胞数目增多,水肿减轻,核膜平整。结论  心脑舒通胶囊可抑制铁死
          亡,减轻CIRI,其作用机制可能与激活Nrf2/HO-1/GPX4信号通路有关。
          关键词  心脑舒通胶囊;脑缺血再灌注损伤;铁死亡;Nrf2/HO-1/GPX4信号通路


          Mechanism  of  Xinnao  shutong  capsule  alleviating  cerebral  ischemia-reperfusion  injury  in  rats  by
          regulating ferroptosis
          LI Huani ,LIU Changhe ,GUO Xiaoyan ,ZHONG Xin ,ZHANG Wei ,GE Wenjing (1.  Academy  of
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          Chinese  Medicine,  Henan  Integrative  Medicine  Hospital,  Zhengzhou  450004,  China;2.  Henan  Engineering
          Research Center of Traditional Chinese Medicine Preparation, Zhengzhou 450004, China;3. Dept. of Pharmacy,
          Zhengzhou Cigarette Factory Rehabilitation Hospital, Zhengzhou 450047, China)
          ABSTRACT    OBJECTIVE  To  study  the  mechanism  of  Xinnao  shutong  capsule  alleviating  cerebral  ischemia  reperfusion  injury
         (CIRI) in rats by regulating the ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group, model
          group,  Xinnao  shutong  low-dose,  high-dose  group (220,  440  mg/kg),  Ginkgo  biloba  leaves  extract  group (positive  control,  150
          mg/kg).  Each  group  of  rats  was  orally  administered  with  the  corresponding  medication/normal  saline  for  7  consecutive  days.
          Transient  occlusion  of  the  middle  cerebral  artery  was  adopted  to  induce  the  CIRI  model;  the  samples  were  taken  24  h  after  the
          operation; the cerebral infarction area of rats was detected, and the cerebral infarction rate was calculated. The pathological changes
          of  brain  tissues  were  observed,  and  the  levels  of  lipid  peroxide (LPO),  malondialdehyde (MDA)  and  glutathione (GSH)  in
          cerebral tissue were detected; mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase
          1(HO-1)  and  glutathione  peroxidase  4 (GPX4)  were  all  detected  in  cerebral  tissue  of  rats.  RESULTS  Compared  with  model
          group,  the  cerebral  infarction  rate,  the  content  of  total  iron  in  cerebral  tissue  and  serum  level  of  LPO (except  for  Ginkgo  biloba
          leaves  extract  group  and  Xinnao  shutong  low-dose  group)  were  all  decreased  significantly  in  G.  biloba  leaves  extract  group  and
          Xinnao  shutong  groups (P<0.05  or  P<0.01);  the  serum  level  of  GSH,  the  protein  and  mRNA  expressions  of  Nrf2,  HO-1  and
          GPX4 were all increased significantly (P<0.05 or P<0.01). The pathological damage to brain tissue was reduced, the number of
          nerve  cells  increased,  the  edema  was  alleviated,  and  the  nuclear  membrane  was  flattened.  CONCLUSIONS  Xinnao  shutong
                                                              capsule  can  inhibit  ferroptosis  and  reduce  CIRI,  the
              Δ 基金项目 河南省自然科学基金项目(No.232300421318);河南
          省中医药科学研究专项课题(No.2022ZY1148);河南省基本科研业务               mechanism  of  which  may  be  associated  with  the  activation  of
          费(No.2304013,No.2404044)                            the Nrf2/HO-1/GPX4 signaling pathway.
             *第一作者 助理研究员,硕士。研究方向:中药药效物质基础。                    KEYWORDS    Xinnao  shutong  capsule;  cerebral  ischemia-
          E-mail:mgmlhn@163.com
                                                              reperfusion  injury;  ferroptosis;  Nrf2/HO-1/GPX4  signaling
              #  通信作者 副 研 究 员 。 研 究 方 向 :中 药 药 理 。 E-mail:
          liuchhn371@163.com                                  pathway


          · 306 ·    China Pharmacy  2025 Vol. 36  No. 3                               中国药房  2025年第36卷第3期
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