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苦参醇F对溃疡性结肠炎小鼠的干预作用
                                                                          Δ


          何旭东 ,倪皓雨,何金彪,李 敏,胡蕴铠,龚弟鸿,姚金铃,俞 捷 ,杨兴鑫 (云南中医药大学中药学院,
                                                                                 #b
                *
                                                                        #a
          昆明 650500)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2024)04-0419-06
          DOI  10.6039/j.issn.1001-0408.2024.04.07


          摘  要  目的  探究苦参醇F(KSC-F)对溃疡性结肠炎(UC)小鼠的干预作用。方法  将30只雄性C57BL/6J小鼠随机分为正常组、
          模型组、阳性对照组(柳氮磺吡啶,703 mg/kg)、KSC-F 50 mg/kg 组(KSC-F50 组)、KSC-F 100 mg/kg 组(KSC-F100 组),每组 6 只。
          除正常组外,其余各组小鼠均连续饮用3%葡聚糖硫酸钠水溶液7 d以复制UC模型;与此同时,各药物组灌胃相应药液,每天1次,
          连续10 d。实验期间,观察小鼠体重变化及排便情况,并于末次给药后进行疾病活动指数评分,观察其结肠组织病理形态,检测血
          清和结肠组织中炎症因子水平,以及结肠组织中炎症因子 mRNA 和炎症相关蛋白[白细胞介素 1β(IL-1β)、叉头框蛋白 O1
         (FOXO1)、磷脂酰肌醇 3 激酶(PI3K)、磷酸化 PI3K(p-PI3K)、p38 丝裂原激活的蛋白激酶(p38 MAPK)、磷酸化 p38 MAPK(p-
          p38 MAPK)、磷酸化蛋白激酶B(p-Akt)等]的表达水平。结果  KSC-F能缓解UC小鼠的体重减轻和结肠组织病变;可不同程度地
          降低血清中IL-1β、IL-6、IL-8、肿瘤坏死因子α(TNF-α)水平和结肠组织中IL-1β、IL-6、IL-17、TNF-α水平,升高血清和结肠组织中
          IL-10 水平(P<0.05 或 P<0.01);可不同程度地降低结肠组织中 IL-1β、IL-17、TNF-α mRNA 和 p-PI3K、p-p38 MAPK、p-Akt蛋白
          的表达水平,提高结肠组织中IL-10 mRNA和FOXO1蛋白的表达水平(P<0.05或P<0.01)。结论  KSC-F可通过抑制PI3K、Akt、
          p38 MAPK蛋白的激活,抑制IL-1β、IL-6、TNF-α等促炎因子的释放,促进抗炎因子IL-10的分泌,减轻结肠组织炎症损伤,从而改
          善UC小鼠的相关症状。
          关键词  苦参醇F;溃疡性结肠炎;炎症反应;干预作用

          Intervention effect of kushenol F on ulcerative colitis mice
          HE Xudong,NI Haoyu,HE Jinbiao,LI Min,HU Yunkai,GONG Dihong,YAO Jinling,YU Jie,YANG Xingxin
         (College of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China)

          ABSTRACT   OBJECTIVE  To  investigate  the  intervention  effect  of  kushenol  F (KSC-F)  on  ulcerative  colitis (UC)  mice.
          METHODS  Totally  30  male  C57BL/6J  mice  were  randomly  divided  into  the  normal  group,  model  group,  positive  drug  group
         (sulfasalazine, 703 mg/kg), KSC-F 50 mg/kg group (KSC-F50 group), and KSC-F 100 mg/kg group (KSC-F100 group), with 6
          mice in each group. Except for the normal group, the mice in the remaining groups were given 3% dextran sulfate sodium solution
          continuously  for  7  days  to  induce  UC  model.  Concurrently,  administration  groups  received  corresponding  drug  solution
          intragastrically, once a day, for 10 consecutive days. During the experiment, the changes in body weight and bowel movements of
          the  mice  were  observed.  Disease  activity  index  scoring  was  performed  after  the  last  administration.  The  histopathological
          morphology  of  colonic  tissue  was  examined.  The  levels  of  inflammatory  factors  in  the  serum  and  colon  tissue  were  measured.
          Additionally,  the  mRNA  expression  of  inflammatory  factors,  and  the  protein  expressions  of  inflammation-related  proteins
          [interleukin-1β (IL-1β),  forkhead  box  O1(FOXO1),  phosphoinositide  3-kinase(PI3K),  phosphorylated  PI3K(p-PI3K),  p38
          mitogen-activated protein kinase(p38 MAPK), phosphorylated p38 MAPK(p-p38 MPAK) and phosphorylated protein kinase B(p-
          Akt)] were determined in colonic tissue. RESULTS KSC-F could alleviate weight loss and colonic tissue damage in UC mice. KSC-
          F reduced the levels of IL-1β, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) in serum, as well as IL-1β, IL-6, IL-17 and TNF-
          α  in  colonic  tissue  to  varying  degrees  and  increased  the  levels  of  IL-10  in  both  serum  and  colonic  tissue (P<0.05  or  P<0.01).
          Moreover, KSC-F decreased the expression levels of IL-1β, IL-17 and TNF-α mRNA, as well as p-PI3K, p-p38 MAPK, and p-
          Akt  proteins  in  colonic  tissue  to  varying  degrees,  and  increased  the  expression  levels  of  IL-10  mRNA  and  FOXO1  protein  in
                                                             colonic  tissue (P<0.05  or  P<0.01).  CONCLUSIONS  KSC-
             Δ  基金项目 国 家 自 然 科 学 基 金 项 目(No. 82104381,No.
                                                             F  effectively  alleviates  UC  symptoms  in  mice  by  inhibiting
          82060707);云南省南药可持续利用研究重点实验室科技人才和平台
                                                             PI3K,  Akt  and  p38  MAPK  activation,  mitigating  the  release
          计划(No.202105AG070012)
                                                             of  pro-inflammatory  factors  such  as  IL-1β,  IL-6,  TNF- α,
             *第一作者 博士研究生。研究方向:中药药效物质研究。
                                                             promoting  the  anti-inflammatory  factor  IL-10  secretion,  and
          E-mail:2758251701@qq.com
                                                             reducing inflammation-induced colonic tissue damage.
             #a 通信作者 教授,博士生导师。研究方向:中药防治代谢性疾
          病。E-mail:yujie@ynutcm.edu.cn                       KEYWORDS     kushenol  F;  ulcerative  colitis;  inflammatory
             #b 通信作者 教授,博士生导师。研究方向:中药药效物质分析。                 reaction; intervention effect
          E-mail:yxx78945@163.com


          中国药房  2024年第35卷第4期                                                 China Pharmacy  2024 Vol. 35  No. 4    · 419 ·
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