Page 38 - 《中国药房》2026年10期
P. 38

柴芪益肝颗粒通过铁死亡途径抗肝癌的作用机制研究
                                                                                             Δ


                 1*
                                                                    4 #
                                           4
                                                    4
                                                            5
                                   3
          刘博文 ,马贵萍 ,李 峰 ,李晓斌 ,卢芬萍 ,庞 旭 ,胡世平 [1.北京中医药大学深圳医院(龙岗)治未病
                           2
          科,广东 深圳 518172;2.北京中医药大学深圳医院(龙岗)中心实验室,广东 深圳 518172;3.南方医科大学
          南方医院消化科,广州 510515;4.北京中医药大学深圳医院(龙岗)肝病科,广东 深圳 518172;5.北京中医药
          大学第一临床医学院,北京 100700]
          中图分类号  R966      文献标志码  A      文章编号  1001-0408(2026)10-1272-05
          DOI  10.6039/j.issn.1001-0408.2026.10.06

          摘   要  目的  探讨柴芪益肝颗粒通过铁死亡途径抗肝癌的作用机制。方法  采用网络药理学方法,结合铁死亡数据库,筛选柴芪
          益肝颗粒调控铁死亡抗肝癌的关键靶点与主要有效成分;运用分子对接技术分析主要有效成分与关键靶点的结合能力。将人肝
          癌Huh-7细胞分为空白血清对照(CON)组、柴芪益肝颗粒含药血清(CQYGKL)组、铁死亡诱导剂(RSL3)组、哺乳动物雷帕霉素靶
          蛋白复合物1(mTORC1)抑制剂(RMC-5552)组、mTORC1激动剂(CCT007093)组及CCT007093+CQYGKL组,检测前3组细胞中
          Fe 、丙二醛(MDA)及谷胱甘肽(GSH)水平,所有组细胞中哺乳动物雷帕霉素靶蛋白(mTOR)、哺乳动物固醇调节元件结合蛋白1
            2+
         (SREBP1)、硬脂酰辅酶A去饱和酶1(SCD1)mRNA表达和SREBP1、SCD1蛋白表达以及mTOR、核糖体S6激酶(S6K)蛋白磷酸
          化水平。结果  柴芪益肝颗粒通过铁死亡途径抗肝癌的关键靶点有 mTOR、SREBP1、SCD1 等,主要有效成分有槲皮素、丹参酮
          ⅡA、黄芩素,主要有效成分与关键靶点的结合能均小于-5 kJ/mol。与CON组比较,CQYGKL组和RSL3组细胞中Fe 、MDA水平
                                                                                                   2+
          均显著升高,GSH水平均显著降低(P<0.05);CQYGKL组、RSL3组、RMC-5552组细胞中mTOR、SREBP1、SCD1 mRNA表达量和
          SREBP1、SCD1蛋白表达量以及mTOR、S6K蛋白磷酸化水平均显著降低,CCT007093组细胞中上述指标均显著升高(P<0.05)。
          而相较CCT007093组,CCT007093+CQYGKL组细胞的上述指标变化均被显著抑制(P<0.05)。结论  柴芪益肝颗粒可能通过抑
          制mTORC1/SREBP1/SCD1轴诱导铁死亡,从而发挥抗肝癌作用。
          关键词  柴芪益肝颗粒;肝癌;铁死亡;mTORC1/SREBP1/SCD1轴;网络药理学;分子对接

          Research on the mechanism of Chaiqi yigan granules against liver cancer via the ferroptosis pathway
          LIU Bowen ,MA Guiping ,LI Feng ,LI Xiaobin ,LU Fenping ,PANG Xu ,HU Shiping [1.  Dept.  of  Preventive
                                                                            5
                    1
                                                                  4
                                          3
                                 2
                                                                                         4
                                                     4
          Treatment  of  Disease,  Beijing  University  of  Chinese  Medicine  Shenzhen  Hospital (Longgang),  Guangdong
          Shenzhen  518172,  China;2.  Central  Laboratory,  Beijing  University  of  Chinese  Medicine  Shenzhen  Hospital
         (Longgang),  Guangdong  Shenzhen  518172,  China;3.  Dept.  of  Gastroenterology,  Nanfang  Hospital,  Southern
          Medical University, Guangzhou 510515, China;4. Dept. of Hepatology, Beijing University of Chinese Medicine
          Shenzhen Hospital (Longgang), Guangdong Shenzhen 518172, China;5. The First School of Clinical Medicine,
          Beijing University of Chinese Medicine, Beijing 100700, China]
          ABSTRACT    OBJECTIVE  To  explore  the  mechanism  of  Chaiqi  yigan  granules (CQYG)  against  liver  cancer  through  the
          ferroptosis  pathway.  METHODS  Network  pharmacology  combined  with  ferroptosis-related  database  was  used  to  screen  key  targets
          and  main  effective  components  of  CQYG  against  liver  cancer  via  regulating  ferroptosis;  molecular  docking  technology  was
          employed to analyze the binding ability of main active components to key targets. Human liver Huh-7 cells were divided into blank
          serum  control (CON)  group,  CQYG  drug-containing  serum (CQYGKL)  group,  ferroptosis  inducer (RSL3)  group,  mammalian
          target  of  rapamycin  complex  1  (mTORC1)  inhibitor  (RMC-5552)  group,  mTORC1  agonist  (CCT007093)  group,  and
          CCT007093+CQYGKL  group. The  levels  of  Fe ,  malondialdehyde (MDA),  and  glutathione (GSH)  in  the  cells  were  detected  in
                                              2+
          the former three groups; mRNA expressions of mammalian target of rapamycin (mTOR), sterol regulatory element-binding protein
          1 (SREBP1), and stearoyl-CoA desaturase 1 (SCD1), protein expressions of SREBP1 and SCD1 as well as phosphorylation levels
          of  mTOR  and  ribosomal  S6  kinase (S6K)  proteins  were  detected  in  all  groups.  RESULTS  Key  targets  of  CQYG  for  anti-liver
          cancer  through  the  ferroptosis  pathway  were  mTOR,  SREBP1,  SCD1,etc.  The  main  active  components  included  quercetin,
                                                              tanshinone  ⅡA,  baicalein,  etc.  The  binding  energies  of  main
              Δ 基金项目 广东省自然科学基金面上项目(No.2025A1515011796);       active components to key targets were all less than -5 kJ/mol.
          深圳市引进中医药高层次医学团队立项项目(No.SZZYSM202311018)             Compared with CON group, the levels of Fe  and MDA in the
                                                                                                2+
             *第一作者 主治医师,博士。研究方向:中医药防治肝癌。E-
                                                              cells  in  CQYGKL  group  and  RSL3  group  were  significantly
          mail:drliubowen@163.com
              # 通信作者 教授,博士。研究方向:中医药防治肝癌。E-mail:               increased,  while  the  levels  of  GSH  were  significantly
          2078200488@qq.com                                   decreased (P<0.05).  mRNA  expressions  of  mTOR,  SREBP1


          · 1272 ·    China Pharmacy  2026 Vol. 37  No. 10                            中国药房  2026年第37卷第10期
   33   34   35   36   37   38   39   40   41   42   43