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马钱苷对脓毒症大鼠炎症反应及肠道屏障损伤的影响
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          王 灿    1, 2* ,李岩涛 ,周 正 ,王璐鹏 ,高媛媛 ,范少希 (1. 河北省中医院重症医学科,石家庄
                             1, 2
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          050011;2.河北中医药大学临床医学院,石家庄 050011;3.河北省中医院药学部,石家庄 050011;4.河北省中
          医院血管外科,石家庄 050011;5.河北省中医院产科,石家庄 050011;6.河北省中医院感染控制科,石家庄
          050011)

          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2025)05-0574-05
          DOI  10.6039/j.issn.1001-0408.2025.05.12

          摘   要  目的  探讨马钱苷通过调节Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋形成蛋白激酶1(ROCK1)信号通路对脓
          毒症大鼠炎症反应及肠道屏障损伤的影响及机制。方法  采用盲肠结扎和穿刺法建立脓毒症大鼠模型,并随机分为脓毒症组、马
          钱苷低剂量组(50 mg/kg 马钱苷,灌胃)、马钱苷高剂量组(200 mg/kg 马钱苷,灌胃)、阳性对照组(0.2 mg/kg 阿托伐他汀,腹腔注
          射)、马钱苷高剂量+溶血磷脂酸(LPA)组(200 mg/kg马钱苷,灌胃+10 mg/kg RhoA激活剂LPA,腹腔注射),另设假手术组,每组10
          只,每6 h给药1次,连续给药4次。末次给药24 h后,检测大鼠血清中炎症因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、IL-
          1β水平;观察大鼠回肠组织病理学变化并进行Chiu’s肠黏膜损伤评分;检测大鼠回肠组织中D-乳酸、D-氨基酸氧化酶(DAO)、内
          毒素水平,闭锁小带蛋白(ZO-1)、闭锁蛋白(Occludin)阳性染色面积百分比以及RhoA、ROCK1的蛋白相对表达水平。结果  与脓
          毒症组比较,马钱苷低剂量组、马钱苷高剂量组大鼠的 ZO-1、Occludin 阳性染色面积百分比均显著升高,IL-6、TNF-α、IL-1β、
          DAO、D-乳酸、内毒素水平和Chiu’s肠黏膜损伤评分以及RhoA、ROCK1蛋白的相对表达水平均显著降低(P<0.05),大鼠回肠组
          织的破坏程度得到缓解,组织水肿及炎性浸润均明显减轻,且马钱苷高剂量组的改善效果均优于马钱苷低剂量组(P<0.05);与马
          钱苷高剂量组比较,RhoA激活剂LPA可显著逆转上述指标的变化趋势(P<0.05)。结论  马钱苷能减轻脓毒症大鼠炎症反应及肠
          道屏障损伤,其机制与抑制RhoA/ROCK1信号通路有关。
          关键词  马钱苷;脓毒症;RhoA/ROCK1信号通路;炎症反应;肠道屏障损伤

          Effects of loganin on inflammatory response and intestinal barrier damage in septic rats
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          WANG Can ,LI Yantao ,ZHOU Zheng ,WANG Lupeng ,GAO Yuanyuan ,FAN Shaoxi (1.  Dept.  of
          Critical  Care  Medicine,  Hebei  Provincial  Hospital  of  Traditional  Chinese  Medicine,  Shijiazhuang  050011,
          China;2.  Clinical  Medical  College,  Hebei  University  of  Chinese  Medicine,  Shijiazhuang  050011,  China;
          3. Dept. of Pharmacy, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China;
          4. Dept. of Vascular Surgery, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011,
          China;5. Dept. of Obstetrics, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang 050011,
          China;6.  Dept.  of  Infection  Control,  Hebei  Provincial  Hospital  of  Traditional  Chinese  Medicine,  Shijiazhuang
          050011, China)

          ABSTRACT    OBJECTIVE To investigate the effects of loganin on inflammatory response and intestinal barrier damage in septic
          rats  by  regulating  the  Ras  homolog  gene  family  member A (RhoA)/Rho-associated  coiled-coil  forming  protein  kinase  1 (ROCK1)
          signaling pathway. METHODS A sepsis rat model was established by cecal ligation and puncture, and randomly divided into sepsis
          group,  loganin  low-dose  group (50  mg/kg  loganin,  gavage),  loganin  high-dose  group (200  mg/kg  loganin,  gavage),  positive
          control group (0.2 mg/kg atorvastatin, intraperitoneal injection), and loganin high-dose + lysophosphatidic acid (LPA) group (200
          mg/kg  loganin  gavage  and  intraperitoneal  injection  of  10  mg/kg  RohA  activator  LPA).  An  additional  sham  surgery  group  was
          established. Each group consisted of 10 rats, and medications were administered once every 6 hours for 4 times. After 24 hours of
          the last intervention, the levels of serum inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β
          were  detected.  The  pathological  changes  of  ileal  tissue  were  observed  and  Chiu’s  intestinal  mucosal  injury  score  was  also
                                                              performed.   The   levels   of   intestinal   function-lactate
              Δ 基金项目 河北省中医药类科研计划课题(No.2022065,No.             dehydrogenase (D-lactate), D-amino acid oxidase (DAO) and
          2020103)                                            endotoxin, the percentages of zonula occludens-1 protein (ZO-1)
             *第一作者 讲师。研究方向:重症医学。E-mail:mga829@163.
                                                              and  Occludin  positive  staining  area,  as  well  as  protein
          com
              # 通信作者 讲师。研究方向:感染控制。E-mail:lkrc06@163.          expressions  of  RhoA,  and  ROCK1  were  all  detected.
          com                                                 RESULTS  Compared  with  the  sepsis  group,  the  percentages


          · 574 ·    China Pharmacy  2025 Vol. 36  No. 5                               中国药房  2025年第36卷第5期
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