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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 ·