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纳灵宁缓解了与自相关的AMPK-Akt/mTOR通路,以调节炎症和屏障功能,减少DSS诱导的肠纤维化
Ke-Ying Wang1,2, Chun-Xiang Huang1,2, Xiao-Jia Hu3
1Guangxi Key Laboratory of Environmental Exposureomics and Entire Lifecycle Health, Guilin Medical University, No. 1, Zhiyuan Road, Guangxi, Guilin 541100, China.
纳灵宁 (NAR) 在性结肠炎 (UC) 鼠标模型中保护肠道纤维化. 这种天然的黄类化合物通过调节关键分子通路来减少炎症和氧化应激,防止疾病的进展.
科学领域:
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 导致狭窄的肠道纤维化是性结肠炎 (UC) 患者的主要并发症.
- 目前对UC相关纤维化的治疗方法有限,需要新的治疗策略.
研究的目的:
- 在UC小鼠模型中研究宁素 (NAR) 对硫酸 (DSS) 诱导的肠纤维化的保护作用.
- 阐明NAR在结肠中的抗纤维作用背后的分子机制.
主要方法:
- 患有DSS诱导的大肠炎的小鼠被口服纳灵宁 (40 mg/kg).
- 评估了临床症状,组织学损伤,结肠F4/80和MPO水平.
- 分析了血清的促炎细胞因子,NLRP3炎症酶激活,Nrf2/Keap1通路,AMPK-Akt/mTOR通路,自,α-SMA和原-I.
主要成果:
- 在UC小鼠中,纳灵宁治疗显著降低了肠纤维化的临床和组织学迹象.
- NAR降低了结肠炎症标志物 (F4/80,MPO) 和血清前炎性细胞因子.
- NAR抑制了NLRP3炎症酶激活,通过Nrf2/Keap1通路降低了氧化应激,通过AMPK-Akt/mTOR通路增强了自,降低了α-SMA和原-I.
结论:
- 纳灵宁显示出对UC肠道纤维化的发展和进展具有显著的保护作用.
- NAR的治疗潜力在于它通过特定的分子通路调节炎症反应,氧化应激和自的能力.
- 纳灵宁代表了一种有前途的治疗药物,用于治疗性结肠炎中的肠纤维化.
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