Page 44 - 《中国药房》2025年2期

车叶草苷对溃疡性结肠炎大鼠肠上皮细胞焦亡的影响及机制
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徐 超 ，谭小平，李 杰，艾明华，卢月月，刘超勇（荆州市第一人民医院消化内科，湖北 荆州 434000）
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中图分类号 R965；R574.1 文献标志码 A 文章编号 1001-0408（2025）02-0166-06
DOI 10.6039/j.issn.1001-0408.2025.02.06

摘 要 目的 探讨车叶草苷（Asp）对溃疡性结肠炎（UC）大鼠肠上皮细胞焦亡的影响及机制。方法 将雄性SD大鼠随机分为对
照组（Control 组），模型组（UC 组），ASP 低、高剂量组[Asp-L、Asp-H 组，Asp 35、70 mg/（kg·d）]，ASP 高剂量+AMPK 抑制剂 Com‐
pound C组[Asp-H+Compound C组，Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]，每组12只。除Control组外，其余各组均以肠
腔灌入50%乙醇（0.25 mL）+5% 2，4，6-三硝基苯磺酸溶液（2 mL/kg）的方式构建UC模型。造模后，各药物组大鼠灌胃或（和）尾静
脉注射相应药液，每天1次，连续14 d。末次给药后，称定各组大鼠体重，测量其结肠长度，并进行疾病活动指数（DAI）评分、结肠
黏膜损伤指数（CMDI）评分，检测其血清中炎症因子[白细胞介素18（IL-18）、IL-1β、IL-6]水平，观察结肠组织病理改变，检测结肠
组织中焦亡相关蛋白[胱天蛋白酶1（caspase-1）、消皮素D（GSDMD）]及通路相关蛋白[腺苷一磷酸活化的蛋白激酶（AMPK）、硫氧
还蛋白互作蛋白（TXNIP）、NOD样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）]的表达情况。结果 与Control组比较，UC组
大鼠结肠组织结构受损，炎症细胞浸润、水肿明显；体重、结肠长度及 AMPK 蛋白的磷酸化水平均显著降低或缩短（P＜0.05）；
DAI、CMDI评分，血清中炎症因子水平以及结肠组织中caspase-1、GSDMD、TXNIP、NLRP3、ASC蛋白的表达均显著升高或上调
（P＜0.05）。与UC组比较，Asp-L、Asp-H组大鼠结肠组织病理损伤均有所减轻，各定量指标均显著改善（P＜0.05），且Asp-H组的
改善效果更明显（P＜0.05）；Compound C可显著逆转高剂量Asp对UC大鼠上述指标的改善作用（P＜0.05）。结论 Asp可改善UC
大鼠结肠组织炎症性损伤，抑制其肠上皮细胞焦亡，上述作用可能与激活AMPK进而抑制TXNIP/NLRP3信号通路有关。
关键词 车叶草苷；溃疡性结肠炎；肠上皮细胞；焦亡；AMPK/TXNIP/NLRP3信号通路

Effects and mechanism of asperuloside on the pyroptosis of intestinal epithelial cells in rats with ulcerative
colitis
XU Chao，TAN Xiaoping，LI Jie，AI Minghua，LU Yueyue，LIU Chaoyong（Dept. of Gastroenterology， Jingzhou
First People’s Hospital， Hubei Jingzhou 434000， China）

ABSTRACT OBJECTIVE To investigate the effects and mechanism of asperuloside （Asp） on the pyroptosis of intestinal
epithelial cells in rats with ulcerative colitis （UC）. METHODS The male SD rats were randomly divided into Control group，
model group （UC group）， ASP low-dose and high-dose groups [Asp-L， Asp-H groups， Asp 35， 70 mg/（kg·d）]， ASP high-dose
group+AMPK inhibitor Compound C group [Asp-H+Compound C group， Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]， with
12 rats in each group. Except for Control group， the other groups were injected with 50% ethanol （0.25 mL）+5% 2，4， 6-
trinitrobenzene sulfonic acid solution （2 mL/kg） into the intestinal cavity to construct UC model. After modeling， the rats in each
drug group were given corresponding drug solution by gavage or （and） tail vein injection， once a day， for 14 consecutive days.
After the last administration， the weight of rats in each group was measured， and the length of their colons was measured； disease
activity index （DAI） score and colonic mucosal damage index （CMDI） score were performed， and the serum levels of
inflammatory factors （interleukin-18， -1β， -6） were detected. The pathological changes of the colon tissue were observed. The
expressions of pyroptosis-related proteins [caspase-1， gasdermin D （GSDMD）] in colon tissue， and pathway-related proteins such
as adenosine monophosphate-activated protein kinase （AMPK）， thioredoxin-interacting protein （TXNIP）， NOD-like receptor
protein 3 （NLRP3） and apoptosis-associated speck-like protein containing a CARD （ASC） were all detected. RESULTS Compared
with Control group， the colon tissue structure of rats in UC group was damaged， with obvious infiltration of inflammatory cells and
edema. Their body weight， colon length and phosphorylation level of AMPK protein were significantly reduced or shortened； DAI
and CMDI scores， serum levels of inflammatory factors， and the protein expressions of caspase-1， GSDMD， TXNIP， NLRP3 and
ASC in colon tissue were increased or upregulated significantly
Δ 基金项目 湖北省科技计划项目（No.2022BCE009）；湖北省卫生 （P＜0.05）. Compared with UC group， the pathological
健康委科研项目（No.WJ2018H204） damage of colon tissue in rats was relieved in Asp-L and Asp-
＊ 第一作者 副 主 任 医 师 。 研 究 方 向 ：消 化 病 学 。 E-mail：
H groups， and all quantitative indicators were significantly
uocwk4@163.com
# 通信作者 副主任医师，硕士。研究方向：消化病学。E-mail： improved （P＜0.05）； the improvement effect of Asp-H group
x11nry@163.com was more significant （P＜0.05）. Compound C could

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