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白术-木香药对对脾虚腹泻型肠易激综合征大鼠肠道菌群与短链

          脂肪酸代谢的调节作用
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          黎豫川 ,张远哲 ,杨元凤 ,陈礼大 ,徐献梅(1.贵州中医药大学第二附属医院药学部,贵阳 550025;2.贵州
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          中医药大学基础医学院,贵阳 550025)
          中图分类号  R965;R285      文献标志码  A      文章编号  1001-0408(2024)03-0304-07
          DOI  10.6039/j.issn.1001-0408.2024.03.07

          摘   要  目的  探讨白术-木香药对对脾虚腹泻型肠易激综合征(IBS-D)大鼠肠道菌群与短链脂肪酸(SCFAs)代谢的调节作用。
          方法  使用番泻叶灌胃联合束缚刺激构建大鼠脾虚IBS-D模型。将造模成功的大鼠分为模型组、阳性对照组(匹维溴铵1.5 mg/kg)
          和白术-木香药对低、中、高剂量组(0.7、1.4、2.8 g/kg),每组6只;另取6只健康大鼠作为空白对照组。空白对照组与模型组大鼠灌
          胃生理盐水,其余各组灌胃相应药液,每天1次,连续14 d。观察大鼠一般状况,并检测粪便含水量;检测大鼠肠道敏感性[以腹壁
          撤退反射(AWR)阈值评价]和肠道推进率;检测大鼠血清中5-羟色胺(5-HT)、P物质(SP)水平;观察大鼠结肠组织病理变化,检测
          大鼠结肠组织中5-HT3受体(5-HT3R)、5-HT4受体(5-HT4R)、5-HT转运体(SERT)蛋白表达水平。取空白对照组、模型组和白术-
          木香药对高剂量组大鼠粪便样本进行16S rRNA测序分析,并检测粪便中乙酸、丙酸、丁酸的含量。结果  与模型组比较,白术-木
          香药对中、高剂量组大鼠给药7、14 d后的体重,粪便含水量,AWR阈值,结肠组织中5-HT4R、SERT蛋白表达水平均显著升高(P<
          0.05或P<0.01);血清中5-HT、SP水平,肠道推进率(白术-木香药对中剂量组除外),结肠组织中5-HT3R蛋白表达水平均显著降
          低(P<0.01);腹泻缓解,精神状态恢复,结肠组织部分结构恢复;且白术-木香药对高剂量组大鼠肠道菌群的多样性与物种数量有
          所减少,粪便中丁酸含量显著降低(P<0.05)。结论  白术与木香配伍可以改善脾虚IBS-D模型大鼠的肠道动力及肠道敏感性,并
          缓解腹泻,这可能与改善肠道菌群结构变化,降低5-HT表达和丁酸含量以及升高5-HT4R、SERT表达有关。
          关键词  肠易激综合征;白术;木香;5-羟色胺;肠道菌群;短链脂肪酸

          Regulatory  effects  of  couplet  medicinals  of  Atractylodes  macrocephala-Aucklandia  lappa  on  gut  microbiota
          and  short-chain  fatty  acid  metabolism  in  the  irritable  bowel  syndrome  rat  with  spleen  deficiency  and
          diarrhea
          LI Yuchuan ,ZHANG Yuanzhe ,YANG Yuanfeng ,CHEN Lida ,XU Xianmei (1.  Dept.  of  Pharmacy,  the
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          Second  Affiliated  Hospital  of  Guizhou  University  of  Traditional  Chinese  Medicine,  Guiyang  550025,  China;
          2. School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China)
          ABSTRACT    OBJECTIVE  To  investigate  the  regulatory  effects  of  couplet  medicinals  of Atractylodes  macrocephala-Aucklandia
          lappa on gut microbiota and short-chain fatty acids (SCFAs) in the diarrhea-type irritable bowel syndrome (IBS-D) rats with spleen
          deficiency.  METHODS  The  IBS-D  rat  model  with  spleen  deficiency  was  induced  by  intragastric  administration  of  Senna
          alexandrina combined with restraint stimulation. The model rats were divided into model group, positive control group (pinaverium
          bromide 1.5 mg/kg), A. macrocephala-A. lappa low-dose, medium-dose and high-dose groups (0.7, 1.4, 2.8 g/kg), with 6 rats in
          each group. Another 6 healthy rats were taken as the blank control group. The blank control group and the model group were given
          normal  saline  intragastrically,  and  other  groups  were  given  relevant  drug  liquid  intragastrically,  once  a  day,  for  consecutive  14
          days. The  general  characteristics  of  rats  and  fecal  water  content  were  observed,  and  intestinal  sensitivity  [evaluating  by  abdominal
          wall  withdrawal  reflex  (AWR)  threshold]  and  the  intestinal  propulsion  rate  were  determined.  The  serum  levels  of  5-
                                                              hydroxytryptamine(5-HT)and  SP  were  detected,  and  the
              Δ 基金项目 贵州省科技计划项目(No. 黔科合基础-ZK〔2022〕一            pathological  changes  of  colon  tissue  were  observed;  the
          般467);贵州省教育厅高等学校科学研究项目(青年项目)(No.黔教技                 protein expressions of 5-HT-3 receptor(5-HT3R), 5-HT4R and
          〔2022〕217 号);贵州中医药大学学术新苗项目(No. 贵科合学术新苗
                                                              5-HT  transporter(SERT)  in  colon  tissue  of  rats  were  detected.
          〔2023〕-37号)                                         16S  rRNA  sequencing  was  performed  for  the  feces  of  rats  in
             *第一作者 副主任药师,博士。研究方向:方剂配伍规律及临床
                                                              blank  control  group,  model  group  and  A.  macrocephala-A.
          应用。E-mail:531533319@qq.com
              # 通信作者 副教授,博士。研究方向:肠道疾病证治与方剂配伍                  lappa  high-dose  group;  the  contents  of  acetic  acid,  propionic
          运用。E-mail:357984356@qq.com                          acid  and  butyric  acid  in  the  feces  of  the  rats  were  determined.


          · 304 ·    China Pharmacy  2024 Vol. 35  No. 3                               中国药房  2024年第35卷第3期
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