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润肠颗粒对小鼠便秘的改善作用及机制
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          黄梦琴 ,王雪松,甘雨涵,卢诗勤,邓琪琪,朱 青 ,郭 姣(广东药科大学中医药研究院/广东省代谢病中西医
                *
                                                        #
          结合研究中心/糖脂代谢病教育部重点实验室/广东省代谢性疾病中医药防治重点实验室,广州 510006)

          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2024)02-0160-06
          DOI  10.6039/j.issn.1001-0408.2024.02.07


          摘   要  目的  探讨润肠颗粒对小鼠便秘的改善作用及潜在机制。方法  将小鼠随机分为正常对照组、模型组、润肠颗粒低剂量组
         (5 g/kg)、润肠颗粒高剂量组(10 g/kg)和莫沙必利组(0.003 g/kg,阳性对照),每组6只。后4组小鼠灌胃洛哌丁胺(0.004 g/kg),每
          天2次,持续给药3 d后开始药物治疗,正常对照组和模型组小鼠灌胃纯水,各药物组小鼠灌胃相应药物,连续给药7 d。末次给药
          后,测定小鼠粪便含水量和肠道推进率,观察结肠和回肠组织结构以及结肠黏液分泌量,检测结肠组织中酪氨酸激酶受体c-kit、黏
          蛋白2(MUC2)、干细胞因子(SCF)蛋白表达水平以及炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β、诱导型一氧
          化氮合成酶(iNOS)]和促进肠道运动相关因子[神经型一氧化氮合酶(nNOS)、平滑肌肌球蛋白轻链激酶(smMLCK)、5-羟色胺受
          体4(5-HT4R)、MUC2、SCF、c-kit]mRNA表达水平。结果  与模型组比较,润肠颗粒低、高剂量组和莫沙必利组小鼠粪便含水量,肠
          道推进率,结肠组织中c-kit蛋白表达水平和MUC2、SCF蛋白相对表达量以及促进肠道运动相关因子(润肠颗粒低剂量组nNOS
          和SCF除外)mRNA相对表达量均显著增加(P<0.05或P<0.01);炎症因子mRNA相对表达量均显著降低(P<0.05或P<0.01);
          结肠和回肠损伤均改善;润肠颗粒高剂量组小鼠结肠黏液分泌量显著增加(P<0.01)。结论  润肠颗粒具有润肠通便的作用,能够
          改善小鼠便秘,其润肠机制可能与促进结肠黏液分泌和MUC2表达有关,其通便机制可能与激活SCF/c-kit信号通路有关。
          关键词  润肠颗粒;便秘;黏蛋白2;干细胞因子/酪氨酸激酶受体信号通路

          Improvement effects of Runchang granules on the constipation in mice and its mechanism
          HUANG Mengqin,WANG Xuesong,GAN Yuhan,LU Shiqin,DENG Qiqi,ZHU Qing,GUO Jiao(Institute  of
          Chinese  Medicine,  Guangdong  Pharmaceutical  University/Guangdong  Metabolic  Diseases  Research  Center  of
          Integrated  Chinese  and  Western  Medicine/Key  Laboratory  of  Glucolipid  Metabolic  Disorder,  Ministry  of

          Education/Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, China)

          ABSTRACT    OBJECTIVE  To  investigate  the  improvement  effects  of  Runchang  granules  on  the  constipation  in  mice  and  its
          potential  mechanism.  METHODS  The  mice  were  randomly  divided  into  normal  control  group,  model  group,  Runchang  granules
          low-dose  and  high-dose  groups (5,  10  g/kg),  mosapride  group (0.003  g/kg,  positive  control),  with  6  mice  in  each  group.  The
          latter 4 groups were given loperamide intragastrically (0.004 g/kg), twice a day, for 3 consecutive days. Normal control group and
          model  group  were  given  purified  water  intragastrically,  and  administration  groups  were  given  relevant  medicine  intragastrically  for
          7  consecutive  days.  After  the  last  medication,  fecal  moisture  content  and  intestinal  motility  of  mice  were  determined,  while  the
          structures  of  colon  and  ileum,  and  the  secretion  of  colonic  mucus  were  observed.  Protein  expressions  of  tyrosine  kinase  receptor
         (c-kit),  mucin  2 (MUC2)  and  stem  cell  factor (SCF)  were  determined  in  colon;  meanwhile,  the  mRNA  expression  levels  of
          inflammatory  factors  [tumor  necrosis  factor-α (TNF-α),  interleukin-6 (IL-6),  IL-1β,  inducible  nitric  oxide  synthase (iNOS)]  as
          well  as  factors  related  to  promoting  intestinal  motility  [neuronal  nitric  oxide  synthase (nNOS),  smooth  muscle  myosin  light  chain
          kinase (smMLCK), 5-hydroxytryptamine 4 receptor (5-HT4R), MUC2, SCF, c-kit] were determined. RESULTS  Compared with
          model group, the fecal water content, intestinal propulsion rate, protein expression of c-kit in colon, relative expressions of MUC2
          and SCF protein, and mRNA expressions of factors related to promoting intestinal motility (except for nNOS and SCF in Runchang
                                                              granules  low-dose  group)  were  all  increased  significantly  in
              Δ 基金项目 广东省基础与应用基础研究重大项目(No.2019B0-              Runchang  granules  low-dose  and  high-dose  groups,  and
          30302005)                                           mosapride  group (P<0.05  or  P<0.01).  mRNA  expression
             *第一作者 硕士研究生。研究方向:中药药效评价与应用。
                                                              levels of inflammatory factors were decreased significantly(P<
          E-mail:2112048009@gdpu.edu.cn
              # 通信作者 教授,硕士生导师,博士。研究方向:中医药防治代谢                 0.05  or  P<0.01).  Both  colon  and  ileum  injuries  improved,
          性疾病。E-mail:zyq973@hotmail.com                       and the secretion of colon mucus was increased significantly in


          · 160 ·    China Pharmacy  2024 Vol. 35  No. 2                               中国药房  2024年第35卷第2期
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