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| (-)-黄皮酰胺对小鼠实验性性结肠炎的治疗作用及机制研究* |
| Study on the Therapeutic Effect and Mechanism of (-)-Clausenamide on Experimental Colitis in Mice |
| 投稿时间：2026-01-19 修订日期：2026-06-18 |
| DOI： |
| 中文关键词: 黄皮酰胺 溃疡性结肠炎 葡聚糖硫酸钠 p-STAT3 |
| 英文关键词: Clausenamide Ulcerative Colitis Dextran Sulfate Sodium (DSS) p-STAT3 |
| 基金项目:山东省中医药科技项目,山东省自然科学基金-青年基金项目,济宁医学院贺林院士新医学临床转化站科研基金项目 |
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| 中文摘要: |
| 目的 研究传统药用植物活性成分(-)-黄皮酰胺（clausenamide，Clau）对葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导的小鼠溃疡性结肠炎（ulcerative colitis，UC）的治疗作用及潜在机制。方法 将40只BALB/c小鼠随机分为正常对照组、DSS模型组、DSS＋5-ASA（50 mg·kg?1）阳性对照组及DSS＋(-)-Clau（40 mg·kg?1）组。对照组小鼠饮用双蒸水，其他组连续7天饮用4% DSS溶液诱导UC模型，DSS＋5-ASA组及DSS＋(-)-Clau组在第1天UC造模的同时灌胃给药，连续给药10天，对照组和DSS组给予生理盐水灌胃。期间监测小鼠一般状况、体重、粪便情况并计算疾病活动指数（disease activity index，DAI）。第11天取血后处死小鼠，提取腹腔巨噬细胞（Mφs），测量结肠长度，称重并计算各主要脏器系数，采用H&E染色观察结肠组织结病理变化、采用ELISA法测定血清和结肠组织中炎症因子的水平、Western blot检测结肠组织中p-STAT3表达。体外构建Mφs与小鼠结肠上皮细胞（MCECs）共培养体系，划痕实验观察(-)-Clau对MCECs迁移能力的影响。结果 实验结果显示，与DSS组相比，(-)-Clau显著改善小鼠一般状况，抑制体重下降（P < 0.01），降低DAI评分，逆转结肠缩短（P < 0.01）及结肠组织病理学损伤，降低脾脏系数回降（P < 0.05）。血清及结肠组织中IL-6、IL-1β、TNF-α含量显著下降（P < 0.05 或 P < 0.01）。Western blot显示Clau明显下调结肠p-STAT3表达（P < 0.01）。共培养实验和细胞划痕实验显示，Clau处理小鼠来源的Mφs能显著增强MCEC的迁移能力（P < 0.01）。结论 研究结果表明(-)-Clau对DSS诱导的小鼠UC具有显著保护作用，其机制可能与抑制p-STAT3介导的炎症信号、促进肠上皮细胞迁移及肠黏膜修复密切相关，提示其作为新型UC治疗候选小分子药物的潜在价值。 |
| 英文摘要: |
| Objective To investigate the therapeutic potential and underlying mechanisms of (-)-clausenamide (Clau), a bioactive constituent derived from the traditional medicinal plant Clausena lansium, in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. Methods Forty BALB/c mice were randomly assigned to four groups: (1) Control, (2) DSS model, (3) DSS + 5-ASA (50 mg kg?1, positive control), and (4) DSS + (-)-Clau (40 mg kg?1). Mice in all groups except Control received 4 % DSS in drinking water for 7 days to establish acute UC. Concurrently, animals were gavaged daily for 10 days with vehicle (Control and DSS groups), 5-ASA, or (-)-Clau. Body weight, stool consistency, and rectal bleeding were monitored daily to calculate the disease activity index (DAI). On day 11, blood was collected, mice were euthanized, and peritoneal macrophages (Mφs) were harvested. Colon length and major organ weights were recorded for organ coefficient calculation. Histopathological changes in colonic tissue were assessed by H&E staining. Levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in serum and colon were determined by ELISA. Expression of phospho-STAT3 (p-STAT3) in colonic tissue was analyzed by Western blot. In parallel, an in vitro co-culture system of Mφs and mouse colonic epithelial cells (MCECs) was established; MCEC migration was evaluated by wound-healing assay. Results Compared with the DSS group, (-)-Clau markedly ameliorated clinical symptoms, attenuated weight loss (P < 0.01), reduced DAI scores, reversed colon shortening (P < 0.01), and mitigated histological damage. Splenomegaly was significantly alleviated (P < 0.05). (-)-Clau decreased IL-6, IL-1β, and TNF-α levels in both serum and colonic tissue (P < 0.05 or P < 0.01). Western blot analysis revealed a significant down-regulation of p-STAT3 expression in colonic mucosa (P < 0.01). In co-culture studies, Mφs pre-treated with (-)-Clau significantly enhanced MCEC migration (P < 0.01). Conclusions Collectively, our findings demonstrate that (-)-clausenamide exerts potent protective effects against DSS-induced UC by inhibiting p-STAT3-mediated inflammatory signaling and promoting intestinal epithelial repair. These results highlight (-)-Clau as a promising small-molecule candidate for future UC therapy. |
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