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芍药甘草汤调控ASIC3/ERK信号通路改善慢传输型便秘大鼠肠

          道动力的机制研究
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          张紫麒    1, 2* ,周鸿雲 ,赵 琼 ,邓 媛 ,赵梦洁 ,赵 辰 ,陈静仪 (1.成都中医药大学附属医院儿科,成都
          610075;2.成都中医药大学临床医学院,成都 611137;3.重庆中医药学院,重庆 402760;4.成都中医药大学药
          学院,成都 611137)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2025)15-1852-07
          DOI  10.6039/j.issn.1001-0408.2025.15.06


          摘   要  目的  探讨芍药甘草汤调控酸敏感离子通道3(ASIC3)/胞外信号调节激酶(ERK)信号通路改善慢传输型便秘(STC)大鼠
          肠道动力的作用机制。方法  SD大鼠采用复方地芬诺酯灌胃构建STC模型,将造模成功大鼠随机分为模型组、芍药甘草汤组(1.5
          g/mL)、乳果糖组(208.4 mg/mL,阳性对照)、联合抑制组(芍药甘草汤1.5 g/mL+盐酸阿米洛利20 μg/kg),每组12只,另取12只健
          康大鼠作为空白组;每天给药1次,连续干预14 d。干预完成后检测大鼠肠道传输功能、内脏敏感性,采用免疫组化染色观察大鼠
          结肠组织中ASIC3的表达,检测大鼠结肠组织中ASIC3、ERK1、ERK2 mRNA的表达和ASIC3、ERK1/2、磷酸化ERK1/2(p-ERK1/2)
          蛋白的表达;观察大鼠结肠肠神经调节系统(ENS)-Cajal 间质细胞(ICC)-平滑肌细胞(SMC)网络超微结构变化。结果  与模型
          组比较,芍药甘草汤组大鼠肠道推进率显著升高,内脏痛阈值显著降低,结肠组织中ASIC3阳性面积占比显著升高,结肠组织中
          ERK1、ERK2、ASIC3 mRNA相对表达量和p-ERK1/2、ASIC3蛋白相对表达量以及p-ERK1/2与ERK1/2比值均显著升高(P<0.05
          或 P<0.01);ICC、SMC 形态结构明显修复,缝隙连接更加紧密。与芍药甘草汤组比较,联合抑制组大鼠肠道动力的改善效果减
          弱,部分指标水平差异有统计学意义(P<0.05或P<0.01);ICC、SMC形态结构的修复作用明显减弱。结论  芍药甘草汤可有效改
          善STC大鼠肠道传输功能并促进肠道修复,其作用机制可能与调控ASIC3/ERK信号通路介导ENS-ICC-SMC网络从而改善肠道
          动力、降低内脏敏感性有关。
          关键词  慢传输型便秘;芍药甘草汤;酸敏感离子通道3;胞外信号调节激酶;ENS-ICC-SMC网络

          Study  on  the  mechanism  of  Shaoyao  gancao  decoction  in  improving  intestinal  motility  in  rats  with  slow
          transit constipation by regulating the ASIC3/ERK signaling pathway
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          ZHANG Ziqi ,ZHOU Hongyun ,ZHAO Qiong ,DENG Yuan ,ZHAO Mengjie ,ZHAO Chen ,CHEN Jingyi            1, 2
                                                    1, 2
         (1.  Dept.  of  Pediatrics,  Hospital  of  Chengdu  University  of  Traditional  Chinese  Medicine,  Chengdu  610075,
          China;2.  Clinical  Medical  College,  Chengdu  University  of  Traditional  Chinese  Medicine,  Chengdu  611137,
          China;3.  Chongqing  College  of  Traditional  Chinese  Medicine,  Chongqing  402760,  China;4.  School  of
          Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China)
          ABSTRACT    OBJECTIVE  To  explore  the  mechanism  of  Shaoyao  gancao  decoction  in  improving  intestinal  motility  in  rats  with
          slow  transit  constipation (STC)  by  regulating  acid-sensitive  ion  channel  3 (ASIC3)/extracellular  signal-regulated  kinase (ERK)
          signaling  pathway.  METHODS  SD  rats  were  used  to  construct  an  STC  model  by  gavage  with  compound  diphenoxylate.  The
          successfully modeled rats were randomly divided into model group, Shaoyao gancao decoction group (1.5 g/mL), lactulose group
         (208.4 mg/mL, positive control), and combined inhibition group (Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20
          μg/kg),  with  12  rats  in  each  group.  Additionally,  12  healthy  rats  were  selected  as  the  blank  group.  They  were  given  relevant
          medicine  once  a  day  and  continuously  intervened  for  14  days.  After  intervention,  the  intestinal  propulsion  function  and  visceral
          sensitivity  of  the  model  rats  were  detected.  The  expression  of  ASIC3  in  the  colon  tissue  of  rats  was  observed  by
                                                              immunohistochemical  staining.  mRNA  expressions  of  ASIC3,
              Δ 基金项目 国家自然科学基金项目(No.82405479);成都中医药            ERK1  and  ERK2  as  well  as  protein  expressions  of  ASIC3,
          大学“杏林学者”学科人才科研提升计划(No.QJRC2024015)                  ERK1/2  and  phosphorylated  ERK1/2 (p-ERK1/2)  in  colon
             *第一作者 博士研究生。研究方向:小儿脾胃系统疾病的中医药
                                                              tissue  of  rats  were  detected;  the  ultrastructural  changes  of  the
          防治。E-mail:727821391@qq.com
                                                              enteric  nervous  system  (ENS) -interstitial  cell  of  Cajal
              # 通信作者 主治医师,博士。研究方向:小儿肺脾系统常见病的
          中医防治。E-mail:echohongyun@163.com                    (ICC)-smooth  muscle  cell (SMC)  network  in  the  rat  colon


          · 1852 ·    China Pharmacy  2025 Vol. 36  No. 15                            中国药房  2025年第36卷第15期
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