海内索尔通过抑制Src介导的NF-κB和化学信号通路来减轻DSS诱导的性结肠炎
Yun-Xia Li1, Jinzhong Liu2, Fang Li3
1Anorectal Department, The People's Hospital of Huaiyin.Jinan, Jinan, Shandong, 250021, China.
Cell biochemistry and biophysics
|July 8, 2024
概括
醇来自于Atractylodes lancea,通过减少炎症和氧化损伤,有效地减轻小鼠的性结肠炎 (UC) 症状. 它通过抑制Src介导的NF-κB信号通路而起作用,为UC患者提供了潜在的治疗方法.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 性结肠炎 (UC) 是一种慢性炎症性肠病,其特点是炎症,氧化损伤和肠道屏障功能受损.
- 目前对UC的治疗方法可能有局限性,需要探索新型治疗剂.
- 醇是一种来自Atractylodes lancea的素,已显示出抗炎性质.
研究的目的:
- 在小鼠模型中研究hinesol对硫酸 (DSS) 诱导的性结肠炎 (UC) 的治疗作用.
- 阐明hinesol在UC作用的潜在分子机制,重点关注炎症和氧化应激途径.
- 评估海内索尔对肠道屏障完整性和免疫细胞反应的影响.
主要方法:
- 使用硫酸 (DSS) 诱导了一种性结肠炎 (UC) 鼠标模型,并使用RAW264.7细胞的脂多糖 (LPS) 刺激建立了一个细胞炎症模型.
- 通过监测疾病活动指数 (DAI),体重,结肠长度和肠道病理学来评估疾病的严重程度.
- 使用ELISA,试剂套件和西部涂抹,量化了促炎细胞因子 (IL-1β,IL-18,IL-6,TNF-α),氧化应激标志物 (SOD,GSH-px,CAT,MDA) 和关键蛋白质 (p-NF-κB P65,p-IκBα,ZO-1,Occludin,Claudin-1,Src) 的水平.
主要成果:
- 醇治疗显著改善了DSS诱导的大肠炎,改善了体重,减少了DAI,并恢复了结肠长度和肠道形态.
- 在DSS小鼠中,海内索尔抑制了高水平的促炎细胞因子 (TNF-α,IL-18,IL-1β,IL-6) 和氧化应激标志物 (MDA),同时增强了抗氧化酶 (SOD,GSH-px,CAT).
- 海内索尔抑制了Src,p-NF-κB P65,p-IκBα和化学因子 (XCL1,CCL2,CXCL16) 的表达,并改善了肠道屏障蛋白 (ZO-1,Occludin,Claudin-1). 分子对接表明hinesol与Src结合,Src过度表达部分逆转了hinesol的保护作用.
结论:
- 醇通过减轻炎症,氧化应激和屏障功能障碍来减轻性结肠炎 (UC) 的显著治疗潜力.
- 该机制涉及对Src介导的NF-κB信号通路和相关的化学激素信号的抑制.
- 醇代表了一种有前途的天然化合物,用于开发新型治疗UC等炎症性肠病的新疗法.
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