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芍药苷对溃疡性结肠炎小鼠氧化应激的影响及机制
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代 鑫 ,王 莹 ,任鑫悦 ,范丁兴 ,李贤哲 ,冯嘉轩 ,娄石磊 ,阎 慧 ,孙 聪 (1.长春中医药大学药学院,
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长春 130117;2.长春中医药大学临床医学院,长春 130117)
中图分类号 R965;R285.5 文献标志码 A 文章编号 1001-0408(2025)04-0427-07
DOI 10.6039/j.issn.1001-0408.2025.04.07
摘 要 目的 基于腺苷一磷酸活化的蛋白激酶(AMPK)/核转录因子红系2相关因子2(Nrf2)通路,探讨芍药苷对小鼠溃疡性结
肠炎(UC)氧化应激的影响及潜在机制。方法 将雄性BALB/c小鼠随机分为对照组,模型组,抑制剂组(AMPK抑制剂Compound
C 20 mg/kg),芍药苷低、中、高剂量组(芍药苷12.5、25、50 mg/kg)、芍药苷高+抑制剂组(芍药苷50 mg/kg+Compound C 20 mg/kg),
每组8只。除对照组外,其余各组小鼠均自由饮用4%葡聚糖硫酸钠溶液5 d以构建UC模型。随后,各药物组小鼠灌胃或腹腔注
射相应药液,每天1次,连续7 d。实验期间,记录各组小鼠体重的变化情况;末次给药24 h后,检测其结肠长度,结肠组织中丙二
醛(MDA)含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,观察其结肠组织病理学形态、肠上皮细胞间紧密
连接情况并进行组织病理学评分,检测其结肠组织中 AMPK、Nrf2 mRNA 及 AMPK、Nrf2、血红素加氧酶 1(HO-1)、闭合蛋白
(occludin)、密封蛋白1(claudin-1)蛋白的表达情况。结果 与模型组比较,芍药苷各剂量组小鼠结肠组织中炎症细胞浸润、隐窝受
损等病理改变均有所恢复,肠上皮细胞间紧密连接受损情况均有所改善;其体重,结肠长度,SOD、GSH-Px活性,以及AMPK蛋白
的磷酸化水平,Nrf2、HO-1、occludin、claudin-1蛋白和AMPK、Nrf2 mRNA的表达均显著升高、延长或上调,MDA含量及组织病理
学评分均显著降低(P<0.05或P<0.01),而抑制剂组上述指标与模型组相当(P>0.05)或更差(P<0.05或P<0.01)。加用抑制剂
可显著逆转高剂量芍药苷对上述指标的改善作用(P<0.01)。结论 芍药苷可修复小鼠肠上皮细胞损伤,改善上皮细胞间紧密连
接,并上调相关蛋白、促抗氧化分子的表达和释放,从而改善UC;其作用机制可能与激活AMPK/Nrf2抗氧化通路有关。
关键词 芍药苷;溃疡性结肠炎;氧化应激;AMPK/Nrf2通路
Effects and mechanism of paeoniflorin on oxidative stress of ulcerative colitis mice
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DAI Xin ,WANG Ying ,REN Xinyue ,FAN Dingxing ,LI Xianzhe ,FENG Jiaxuan ,LOU Shilei ,YAN Hui ,
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SUN Cong(1. School of Pharmacy, Changchun University of Chinese Medicine,Changchun 130117,China;
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2. School of Clinical Medicine,Changchun University of Chinese Medicine,Changchun 130117,China)
ABSTRACT OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative
colitis (UC) mice based on adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2
(Nrf2) pathway. METHODS Male BALB/c mice were randomly divided into control group, model group, inhibitor group (AMPK
inhibitor Compound C 20 mg/kg), paeoniflorin low-, medium- and high-dose groups (paeoniflorin 12.5, 25, 50 mg/kg), high-
dose of paeoniflorin+inhibitor group (paeoniflorin 50 mg/kg+Compound C 20 mg/kg), with 8 mice in each group. Except for the
control group, mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model.
Subsequently, mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally, once a day,
for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last
administration, colon length, malondialdehyde (MDA) content, and activities of superoxide dismutase (SOD) and glutathione
peroxidase (GSH-Px) in colon tissues were measured; histopathological morphology of colon tissues, tight junctions between
intestinal epithelial cells, and histopathological scoring were all observed and evaluated; the mRNA expressions of AMPK and
Nrf2, as well as the protein expressions of heme oxygenase-1(HO-1), occludin and claudin-1, were all determined in colon tissue.
RESULTS Compared with model group, paeoniflorin groups exhibited recovery from pathological changes such as inflammatory
cell infiltration and crypt damage in the colon tissue, as well
Δ 基金项目 吉 林 省 自 然 科 学 基 金 项 目(No. YDZJ202401060 as improved tight junction damage between intestinal epithelial
ZYTS);吉林省教育厅科学技术研究项目(No.JJKH20230949KJ);长 cells. Additionally, significant increases or upregulations were
春 中 医 药 大 学 国 家 级 大 学 生 创 新 创 业 训 练 计 划 项 目(No. observed in body weight, colon length, activities of SOD and
202210199023) GSH-Px, phosphorylation level of AMPK, and protein
*第一作者 硕士研究生。研究方向:中药抗炎症性肠病作用机
expression of Nrf2, HO-1, occludin, claudin-1, and mRNA
制。E-mail:1609497176@qq.com
# 通信作者 教授,硕士生导师,博士。研究方向:中药抗常见多发 expressions of AMPK and Nrf2; concurrently, MDA content
病作用机制。E-mail:37363266@qq.com and histopathological scores were significantly reduced (P<
中国药房 2025年第36卷第4期 China Pharmacy 2025 Vol. 36 No. 4 · 427 ·