利多卡因通过调节皮质otropin释放激素受体2来改善刺激性肠综合征的肠壁功能障碍
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Published on: March 26, 2020
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Yanrong Wang1, Mingbiao Qiao2, Xue Yao3
1Department of Laboratory Medicine, Sichuan Tianfu New Area People's Hospital, Chengdu, China.
Neurogastroenterology and motility
|September 22, 2023
概括
利多卡因通过增强肠细胞中的皮质otropin释放激素受体2 (CRHR2) 来有效治疗易怒肠综合征 (IBS) 中的肠道屏障功能障碍. 这种治疗改善了肠道的透性并减少了炎症,为IBS提供了潜在的治疗策略.
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.
- 细胞生物学 细胞生物学
背景情况:
- 肠道屏障功能障碍是各种疾病的关键因素,有效治疗方法有限.
- 利多卡因已经显示出潜在的抗炎作用和降低刺激性肠综合征 (IBS) 中内脏过敏的能力.
研究的目的:
- 为了研究利多卡因在改善肠道屏障功能障碍的有效性,在IBS的小鼠模型中.
- 阐明利多卡因作用的基本机制,重点关注其与皮质otropin释放激素受体2 (CRHR2) 的相互作用.
主要方法:
- 接受避水压力 (WAS) 的老鼠接受了利多卡因治疗,以评估内脏过敏,炎症标志物,肠道透性 (FD4流量) 和紧密结合完整性.
- 在体外研究中使用了用利多卡因治疗的Caco-2细胞来检查CRHR2使用siRNA和对抗剂的作用.
主要成果:
- 在WAS大鼠中,利多卡因治疗逆转了体重减轻,改善了紧结 (TJ) 完整性,并降低了过敏和肠道透性的标志物 (DAO,D-Lac,LPS).
- 利多卡因降低了肠道炎症因子 (IL-1β,IFN-γ,TNF-α),抑制了皮质otropin释放激素 (CRH) 水平,并提高了肠道上皮细胞中的CRHR2表达.
- 在体外,利多卡因增强了Caco-2细胞中的CRHR2表达,恢复了由LPS破坏的屏障功能,这种效果取决于CRHR2活性.
结论:
- 利多卡因在IBS的肠道屏障功能障碍方面显示出显著的治疗潜力.
- 利多卡因的保护作用通过调节肠道上皮细胞上的CRHR2表达来调节.
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