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哈萨克医经典名方吾孜德克治疗肠炎的物质基础及作用机制
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          贾丽萍 ,程 波 ,史玉柱 ,何 江 ,王 雪 ,杨伟俊 (1. 新疆农业大学食品科学与药学学院,乌鲁木齐
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          830004;2.新疆维吾尔自治区药物研究所新疆维吾尔药重点实验室,乌鲁木齐 830004;3.新疆维吾尔自治区
          药物研究所药理Ⅱ实验室,乌鲁木齐 830004)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)13-1577-07
          DOI  10.6039/j.issn.1001-0408.2023.13.07

          摘  要  目的  探讨哈萨克医经典名方吾孜德克(WZDK)治疗肠炎的物质基础及潜在作用机制。方法  利用液相色谱-串联质谱
         (LC-MS/MS)技术分析WZDK中的化学成分。通过网络药理学和分子对接技术筛选WZDK的主要化学成分并进行靶点预测,通
          过体内实验验证WZDK对急性肠炎的治疗作用及作用靶点。采用葡聚糖硫酸钠诱导构建小鼠急性肠炎模型,给药期间观察小鼠
          一般状况并计算疾病活动指数(DAI)评分,通过苏木素-伊红染色、实时荧光定量 PCR 验证各组小鼠肠道病理改变及核心靶点
          mRNA的表达。结果  通过LC-MS/MS技术分析共得到316种化学成分;通过网络药理学分析,核心靶点主要包括白细胞介素1β
         (IL-1β)、蛋白激酶B1(AKT1)、肿瘤蛋白p53(TP53)、IL-6、肿瘤坏死因子(TNF)等;分子对接结果显示,白桦脂酸、lappadilactone、
          木香烃内酯、去氢木香内酯等化学成分与核心靶点结合稳定。体内实验结果显示,与模型组比较,高剂量(5.00 g/kg)WZDK能显
          著降低小鼠的DAI评分(P<0.05),改善其结肠组织炎症细胞浸润、黏膜组织损伤,显著下调其结肠组织中IL-6、TNF-α、IL-1β和
          TP53 mRNA的表达(P<0.05或P<0.01)。结论  WZDK中的白桦脂酸、lappadilactone、木香烃内酯、去氢木香内酯等多种化学成
          分可能通过下调结肠组织中TNF-α、IL-6、IL-1β、TP53 mRNA表达,发挥改善肠道局部炎症因子失衡、修复结肠黏膜组织损伤的作用。
          关键词  吾孜德克;哈萨克医;经典名方;网络药理学;分子对接;肠炎


          Material basis and mechanism of Kazakh classic prescription Wuzdekh in the treatment of enteritis
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          JIA Liping ,CHENG Bo ,SHI Yuzhu ,HE Jiang ,WANG Xue ,YANG Weijun(1.  School  of  Food  Science  and
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          Pharmacy,  Xinjiang  Agricultural  University,  Urumqi  830004,  China;2.  Key  Laboratory  of  Xinjiang  Uygur
          Medicine,  Xinjiang  Institute  of  Materia  Medica,  Urumqi  830004,  China;3.  Laboratory  Ⅱ  of  Pharmacology,
          Xinjiang Institute of Materia Medica, Urumqi 830004, China)
          ABSTRACT   OBJECTIVE  To  explore  the  material  basis  and  potential  mechanism  of  Kazakh  classic  prescription  Wuzdekh
         (WZDK)  in  the  treatment  of  enteritis.  METHODS  LC-MS/MS  technology  was  used  to  analyze  the  chemical  components  in
          WZDK.  Through  network  pharmacology  and  molecular  docking  technology,  the  main  chemical  components  of  WZDK  were
          screened  and  the  target  was  predicted;  therapeutic  effect  and  target  of  WZDK  on  acute  enteritis  were  verified  through  in  vivo
          experiments. The  acute  enteritis  model  of  mice  was  induced  by  dextran  sulfate  sodium  salt;  the  general  condition  of  the  mice  was
          observed during administration and the disease activity index (DAI) score was calculated; pathological changes of the intestine and
          mRNA expression of core target were validated by HE staining and quantitative real-time PCR. RESULTS A total of 316 chemical
          components were obtained by LC-MS/MS. The core targets of network pharmacological analysis mainly included interleukin 1β(IL-
          1β),  protein  kinase  B1 (AKT1),  tumor  protein  p53 (TP53),  IL-6,  tumor  necrosis  factor (TNF)  and  so  on.  The  results  of
          molecular  docking  showed  that  chemical  components  such  as  mairin,  lappadilactone,  costunolide  and  dehydrocostus  lactone  were
          stable  in  binding  to  the  core  target.  The  results  of  in  vivo  experiment  showed  that,  compared  with  model  group,  high  dose (5.00
          g/kg)  of  WZDK  could  significantly  reduce  the  DAI  score (P<0.05),  improve  inflammatory  cell  infiltration  and  mucosal  tissue
          damage of colon tissue, and significantly down-regulated mRNA expressions of IL-6, TNF-α, IL-1β and TP53 in colon tissue(P<
          0.05  or  P<0.01).  CONCLUSIONS  Chemical  components  of  WZDK  such  as  mairin,  lappadilactone,  costunolide  and
          dehydrocostus  lactone  may  play  the  role  of  improving  the  imbalance  of  local  inflammatory  factors  in  the  intestine  and  repairing
                                                             damage  of  colonic  mucosal  tissue  by  down-regulating  mRNA
             Δ 基金项目 新疆维吾尔自治区重大科技专项(No.2022A03003-3)
             *第一作者 硕士研究生。研究方向:中药肠病的作用机制。                     expressions of TNF-α, IL-6, IL-1β and TP53 in colon tissue.
          E-mail:1696515583@qq.com                           KEYWORDS     Wuzdekh;Kazakh  medicine;classic  prescription;
             # 通信作者 研究员,博士生导师,博士。研究方向:新疆地产中药                 network pharmacology; molecular docking; enteritis
          民族药。E-mail:wilfred3106@163.com


          中国药房  2023年第34卷第13期                                              China Pharmacy  2023 Vol. 34  No. 13    · 1577 ·
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