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基于网络药理学和代谢组学的蟾宝痔疮栓抗痔疮的机制研究
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          郭春风 ,蒋 鑫 ,程汝阳 ,刘树民 ,谢春祥 ,卢 芳 (1.黑龙江中医药大学附属第二医院哈南分院中医内
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          科,哈尔滨 150040;2.黑龙江中医药大学中医药研究院,哈尔滨 150040;3.黑龙江蟾宝生物科技发展有限公
          司,黑龙江 鹤岗 154100)
          中图分类号  R965;R285      文献标志码  A      文章编号  1001-0408(2025)13-1622-07
          DOI  10.6039/j.issn.1001-0408.2025.13.12

          摘   要  目的  通过网络药理学和代谢组学探讨蟾宝痔疮栓(CBZCS)对痔疮大鼠的改善作用机制。方法  利用浸吸巴豆油致肛
          门肿胀建立大鼠痔疮模型。将SD大鼠分为空白组(NC组,0.32 g/kg凡士林),模型组(Model组,0.32 g/kg凡士林),CBZCS低、中、
          高剂量组(分别记为CBZCS-L、CBZCS-M、CBZCS-H组,给药剂量分别为0.16、0.32、0.64 g/kg),马应龙麝香痔疮栓组(Positive组,
          0.32 g/kg),每组9只;分别于造模后6、12、24、48、72 h进行肛门给药。末次给药后,观察大鼠肛门组织病理变化,检测大鼠血清中
          白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平。通过代谢组学的方法进行差异代谢物分析和通路富集分析,运用网络药理学
          获得CBZCS治疗痔疮的靶点蛋白,联合差异代谢物和靶点蛋白进行交互和富集分析以筛选核心代谢通路,并对核心蛋白进行实
          验验证。结果  与 NC 组比较,Model 组大鼠肛门组织出现明显病变,血清中 IL-6、TNF-α 水平显著升高(P<0.05);与 Model 组比
          较,给药组大鼠肛门组织病理损伤均有不同程度缓解,CBZCS-H组、CBZCS-M组、Positive组大鼠血清中IL-6水平和CBZCS-H组
          大鼠血清中TNF-α水平均显著降低(P<0.05)。代谢组学结果显示,从大鼠的肛门组织中共筛选出34个差异代谢物,经CBZCS给
          药后共有22个出现回调。回调的差异代谢物主要富集于花生四烯酸代谢、组氨酸代谢和甘油磷脂代谢通路。通过网络药理学的
          方法确定了138个CBZCS抗痔疮的交集基因。差异代谢物和靶点蛋白主要富集于花生四烯酸代谢通路,该通路的调控可能与环
          氧合酶2(COX-2)、Myc原癌基因蛋白(c-MYC)、细胞色素P450 1B1(CYP1B1)、白细胞介素1β(IL-1β)、IL-6的蛋白表达有关。实
          验验证结果显示,Model组大鼠肛门组织中关键蛋白(COX-2、c-MYC、CYP1B1、IL-1β、IL-6)的表达水平均较NC组显著升高(P<
          0.05),CBZCS-H组和Positive组大鼠肛门组织中上述蛋白水平均较Model组显著降低(P<0.05)。结论  CBZCS抗痔疮机制可能
          是抑制COX-2、c-MYC、CYP1B1蛋白的表达,进而抑制花生四烯酸代谢,减少炎症因子IL-6、IL-1β的释放。
          关键词  蟾宝痔疮栓;痔疮;花生四烯酸代谢;环氧合酶2;Myc原癌基因蛋白;细胞色素P450 1B1;炎症反应;代谢组学;网络药理学


          Study  on  mechanism  of  Chanbao  zhichuang  suppository  in  treating  hemorrhoids  based  on  network
          pharmacology and metabolomics
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          GUO Chunfeng ,JIANG Xin ,CHENG Ruyang ,LIU Shumin ,XIE Chunxiang ,LU Fang(1.  Dept.  of  TCM
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          Internal Medicine, Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,
          Harbin  150040,  China;2.  Institute  of  Traditional  Chinese  Medicine,  Heilongjiang  University  of  Chinese
          Medicine, Harbin 150040, China;3. Heilongjiang Chanbao Biotechnology Development Co., Ltd., Heilongjiang
          Hegang 154100, China)
          ABSTRACT    OBJECTIVE  To  explore  the  mechanism  of  improvement  effect  of  Chanbao  zhichuang  suppository (CBZCS)  on
          hemorrhoids  in  rats  through  network  pharmacology  and  metabolomics.  METHODS  A  hemorrhoid  model  was  established  by
          subcutaneous  injection  of  rhododendron  oil  to  induce  anal  swelling.  SD  rats  were  divided  into  blank  group (NC  group,  0.32  g/kg
          vaseline), model group (Model group, 0.32 g/kg vaseline), CBZCS low-, medium-, and high-dose groups (CBZCS-L, CBZCS-
          M,  CBZCS-H  groups,  with  dosages  of  0.16,  0.32,  and  0.64  g/kg  respectively),  and  Mayinglong  musk  hemorrhoids  suppository
          group (Positive group, 0.32 g/kg), with 9 rats in each group. Anal administration was performed at 6, 12, 24, 48, and 72 hours
          after  modeling.  After  the  last  administration,  the  pathological  changes  of  the  anal  tissues  in  rats  were  observed,  and  the  serum
          levels  of  interleukin-6 (IL-6)  and  tumor  necrosis  factor- α (TNF- α)  in  rats  were  detected.  Differential  metabolite  analysis  and
          enrichment  analysis  were  conducted  by  metabolomics  methods,  and  the  target  proteins  of  CBZCS  in  treating  hemorrhoids  were
                                                              obtained  by  network  pharmacology.  The  core  metabolic
              Δ 基金项目 黑龙江省中医药管理局第二批省级名中医专家传承
                                                              pathways were screened by interaction and enrichment analysis
          工作室建设项目
             *第一作者 副主任医师,博士。研究方向:中医药在内科疾病中                    of  differential  metabolites  and  proteins,  and  the  core  proteins
          的应用。E-mail:15004601905@163.com                      were  experimentally  verified.  RESULTS  Compared  with  the
              # 通信作者 研究员,博士生导师,博士。研究方向:中药药性理论                 NC  group,  the  anal  tissues  of  the  Model  group  showed
          及药效物质基础。E-mail:lufang_1004@163.com                  obvious  lesions,  and  the  levels  of  IL-6  and  TNF- α  in  the


          · 1622 ·    China Pharmacy  2025 Vol. 36  No. 13                            中国药房  2025年第36卷第13期
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