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术后通气方对术后肠麻痹小鼠肠道损伤的改善作用及机制
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          卢雨暄 ,江志伟 ,谢怡君 ,王弈竹 ,哈静文 ,束雅春 (1.南京中医药大学附属医院药学部,南京 210029;
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          2.中国药科大学中药学院,南京 211112)
          中图分类号  R965;R285.5      文献标志码  A      文章编号  1001-0408(2024)17-2108-06
          DOI  10.6039/j.issn.1001-0408.2024.17.09
          摘   要  目的  研究术后通气方对术后肠麻痹(POI)小鼠肠道损伤的改善作用及机制。方法  将小鼠随机分为假手术组、模型组、
          阳性对照组(枸橼酸莫沙必利片,1.95 mg/kg)、术后通气方组(1.88 g/kg),每组6只。除假手术组外,其余各组小鼠使用经典小肠干
          扰术制备POI模型。各组小鼠灌胃相应药液/水,每天1次,连续2 d。末次给药后,检测小鼠肠道炭末推进率;观察小鼠回肠组织
          病理形态学变化;检测小鼠血清中白细胞介素6(IL-6)、IL-10、肿瘤坏死因子α(TNF-α)、胃动素(MTL)和生长抑素(SS)水平;检测
          小鼠回肠组织中Toll样受体4(TLR4)、核因子κB p65(NF-κB p65)、p38丝裂原活化蛋白激酶(p38 MAPK)表达水平;分析小鼠结
          肠内容物的肠道菌群结构。结果  经术后通气方干预后,小鼠回肠组织肠壁萎缩、黏膜毛细血管充血等病理损伤明显改善;小肠炭
          末推进率和血清中 IL-10、MTL 水平均显著升高(P<0.05);血清中 TNF-α、IL-6、SS 水平,回肠组织中 TLR4、NF-κB p65、p38
          MAPK蛋白核内表达水平均显著降低(P<0.05)。肠道菌群分析结果显示,术后通气方可显著升高ACE、Chao1、Shannon、PD指数
          以及阿克曼氏菌属(Akkermansia)相对丰度(P<0.05),显著降低变形菌门(Proteobacteria)、酸鱼联合乳杆菌属(Ligilactobacillus)、
          大肠埃希菌属-志贺氏菌属(Escherichia-Shigella)相对丰度(P<0.05)。结论  术后通气方可改善POI小鼠肠道损伤及炎症反应,其
          作用机制可能与抑制TLR4/NF-κB/MAPK信号通路活性,调节胃肠激素水平,改善肠道菌群紊乱有关。
          关键词  术后通气方;术后肠麻痹;肠道损伤;炎症因子;肠道菌群

          Improvement  effect  and  mechanism  of  Shuhou  tongqi  formula  on  intestinal  injury  in  mice  with
          postoperative ileus
          LU Yuxuan ,JIANG Zhiwei ,XIE Yijun ,WANG Yizhu ,HA Jingwen ,SHU Yachun (1.  Dept.  of  Clinical
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          Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China;2. College of
          Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 211112, China)
          ABSTRACT    OBJECTIVE  To  study  the  improvement  effect  and  mechanism  of  Shuhou  tongqi  formula  on  intestinal  injury  in
          mice  with  postoperative  ileus (POI).  METHODS  Mice  were  randomly  divided  into  sham  operation  group,  model  group,  positive
          control group (Mosapride citrate tablets, 1.95 mg/kg), and Shuhou tongqi formula group (1.88 g/kg), with 6 mice in each group.
          Except  for  the  sham  operation  group,  POI  model  was  induced  in  other  groups  by  typical  small  intestinal  interference.  Each  group
          was  given  relevant  drug  liquid/water,  once  a  day,  for  consecutive  2  days.  After  the  last  medication,  the  percentage  of  carbon
          powder  propulsion  in  small  intestine  was  detected,  and  pathomorphological  changes  in  ileum  tissue  of  mice  were  observed.  The
          serum  levels  of  interleukin-6 (IL-6),  IL-10,  tumor  necrosis  factor-α (TNF-α),  motilin (MTL)  and  somatostatin (SS)  were  all
          detected; the expression levels of Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB p65) and p38 mitogen-activated protein
          kinase (p38  MAPK)  were  determined  in  ileal  tissue  of  mice;  the  gut  microbiota  of  colon  contents  was  analyzed  in  each  group  of
          mice. RESULTS After the intervention of Shuhou tongqi formula, pathological damage such as intestinal wall atrophy and mucosal
          capillary congestion in ileum tissue were improved significantly; the percentage of carbon powder propulsion and the serum level of
          IL-10 and MTL were increased significantly (P<0.05); however, serum levels of TNF-α, IL-6 and SS, the expressions of TLR4,
          NF-κB  p65  and  p38  MAPK  were  decreased  significantly (P<0.05).  The  analysis  of  gut  microbiota  showed  that  Shuhou  tongqi
          formula  could  significantly  increase ACE,  Chao1,  Shannon  and  PD  indexes,  and  relative  abundance  of Akkermansia (P<0.05),
          but  decreased  relative  abundance  of  Proteobacteria,  Ligilactobacillus  and  Escherichia-Shigella  significantly  (P<0.05).
          CONCLUSIONS  Shuhou  tongqi  formula  can  improve  intestinal  injury  and  inflammatory  reaction  of  POI  mice,  the  mechanism  of
                                                              which  may  be  associated  with  inhibiting  the  activity  of  TLR4/
              Δ 基金项目 江苏省知识产权高价值专利培育计划项目(No.
                                                              NF- κB/MAPK  signaling  pathway,  regulating  the  levels  of
          GJ20231160_01);南京市医疗机构中药传统制剂研究立项项目(No.
                                                              gastrointestinal  hormones  and  improving  the  disturbance  of
          NJCC-ZJ-202303);南京市知识产权项目
             *第一作者 硕士研究生。研究方向:中药分析与中药药理。                      intestinal flora in mice.
          E-mail:1643589936@qq.com                            KEYWORDS    Shuhou  tongqi  formula;  postoperative  ileus;
              # 通信作者 主任中药师,硕士生导师。研究方向:中药炮制及中                  intestinal injury; inflammatory factor; intestinal flora
          药健康产品研发。E-mail:guzheng0512@163.com


          · 2108 ·    China Pharmacy  2024 Vol. 35  No. 17                            中国药房  2024年第35卷第17期
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