牡荆苷对溃疡性结肠炎小鼠炎症的改善作用及机制
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| 篇名: | 牡荆苷对溃疡性结肠炎小鼠炎症的改善作用及机制 |
| TITLE: | Ameliorative effect and mechanism of vitexin on inflammation in ulcerative colitis mice |
| 摘要: | 目的 探讨牡荆苷对溃疡性结肠炎(UC)小鼠炎症的改善作用及潜在机制。方法以连续饮用3%葡聚糖硫酸钠溶液5d的方式构建UC小鼠模型,并将造模成功的小鼠随机分为UC组,牡荆苷低、高剂量组(牡荆苷-L、牡荆苷-H组,40、80mg/kg),美沙拉嗪组(400mg/kg),牡荆苷-H+重组锯齿样典型Notch配体1(rJagged-1)组(牡荆苷-H+rJagged-1组,80mg/kg牡荆苷+1mg/kgrJagged-1),每组12只;另取12只正常小鼠,作为对照(CK)组。各组小鼠灌胃并腹腔注射相应药液或相应药液和生理盐水,每天1次,连续7d。观察各组小鼠实验期间的一般情况;末次给药24h后,评价各组小鼠的疾病活动指数(DAI)评分,观察结肠组织病理形态并进行病理评分,检测脾脏和结肠组织中巨噬细胞极化水平以及结肠组织中白细胞介素6(IL-6)、IL-10、肿瘤坏死因子α(TNF-α)、转化生长因子β(1TGF-β1)、Jagged-1、Notch1、Notch胞内域(NICD)蛋白的表达量。结果与UC组比较,牡荆苷-L组、牡荆苷-H组、美沙拉嗪组小鼠摄食和饮水减少、毛发无光泽等症状及上皮细胞脱落、炎症细胞浸润等病理改变均明显改善;其DAI评分,结肠组织病理评分,脾脏组织中M1型巨噬细胞含量、M1/M2型巨噬细胞比例,结肠组织中M1型巨噬细胞比例和IL-6、TNF-α、Jagged-1、Notch1、NICD蛋白的表达量均显著降低;脾脏组织中M2型巨噬细胞含量以及结肠组织中M2型巨噬细胞比例和IL-10、TGF-β1蛋白的表达量均显著升高(P<0.05),且牡荆苷-H组、美沙拉嗪组的改善效果显著优于牡荆苷-L组(P<0.05)。与牡荆苷-H组比较,牡荆苷-H+rJagged-1组小鼠上述症状及病理改变均有所加重,各定量指标均显著逆转(P<0.05)。结论牡荆苷对UC小鼠炎症具有改善作用,上述作用与其抑制Jagged-1/Notch1通路、调控巨噬细胞极化(抑制M1型极化、促进M2型极化)有关。 |
| ABSTRACT: | OBJECTIVE To explore the ameliorative effect and potential mechanism of vitexin on inflammation in ulcerative colitis (UC) mice. METHODS The UC mice model was established by continuous administration of 3% dextran sulfate sodium solution for 5 days. Mice with successful modeling were randomly divided into UC group, vitexin low- and high-dose groups (vitexin-L and vitexin-H groups, 40, 80 mg/kg), mesalazine group (400 mg/kg), and vitexin-H+recombinant Jagged canonical Notch ligand 1 (rJagged-1) group (vitexin-H+rJagged-1 group, 80 mg/kg vitexin+1 mg/kg rJagged-1), with 12 mice in each group. Another 12 normal mice were used as the control (CK) group. Mice in each group were administered the corresponding drugs or the corresponding drugs and normal saline by gavage and intraperitoneal injection once daily for 7 consecutive days. General conditions were observed during the experiment. At 24 h after the last administration, the disease activity index (DAI) score was evaluated. Colonic histopathological morphology was observed and scored. Macrophage polarization levels in the spleen and colon tissues were measured. The protein expressions of interleukin-6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α), transforming growth factor-β 1 (TGF-β 1 ), Jagged-1, Notch1 and Notch intracellular domain (NICD) in colonic tissues were determined. RESULTS Compared with the UC group, the symptoms (reduced food and water intake, dull fur, etc.) and pathological changes (epithelial cell shedding, inflammatory cell infiltration, etc.) were significantly improved in the vitexin-L, vitexin-H and mesalazine groups. DAI scores, colonic histopathological scores, M1 macrophage contents in spleen tissue, M1/M2 macrophage ratios, M1 macrophage proportions in colon tissue, and protein expressions of IL-6, TNF-α, Jagged-1, Notch1 and NICD in colon tissue were significantly decreased ( P <0.05). Meanwhile, the M2 macrophage contents in spleen tissue, M2 macrophage proportions in colon tissue, and protein expressions of IL-10 and TGF-β 1 in colon tissue were significantly increased ( P <0.05). Moreover, the improvement effects in the vitexin-H and mesalazine groups were significantly superior to those in the vitexin-L group ( P <0.05). Compared with the vitexin-H group, the above symptoms and pathological changes were aggravated, and all quantitative indicators were significantly reversed in the vitexin-H+rJagged-1 group ( P <0.05). CONCLUSIONS Vitexin can ameliorate the inflammation of UC mice, which is associated with its inhibition of the Jagged-1/Notch1 pathway and regulation of macrophage polarization (inhibition of M1-type polarization and promotion of M2-type polarization). |
| 期刊: | 2026年第37卷第06期 |
| 作者: | 周林;夏鹏飞;刘毓玲;孟志超;李耕;喻媛媛 |
| AUTHORS: | ZHOU Lin,XIA Pengfei,LIU Yuling,MENG Zhichao,LI Geng,YU Yuanyuan |
| 关键字: | 牡荆苷;溃疡性结肠炎;炎症;巨噬细胞;极化;Jagged-1/Notch1通路 |
| KEYWORDS: | vitexin; ulcerative colitis; inflammation; macrophages; polarization; Jagged-1/Notch1 pathway |
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