脱水可斯托斯乳通过阻断TLR4/MD2复合体形成来缓解因虹素诱导的肠粘膜炎
Miaomiao Sun1, Honghong Zhan2, Xiaoliang Long3
1Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China.
脱水乳 (DHL) 通过抑制TLR4/MD2复合体和下游炎症通路,防止化疗引起的肠粘膜炎. 这种天然化合物显示出与义诺太干 (CPT-11) 结合治疗的潜力,以减少胃肠道副作用.
科学领域:
- 药理学 药理学是指药理学的学科.
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 氨酸 (CPT-11) 化疗导致严重的胃肠道毒性,限制了其临床使用.
- 传统中国医学使用奥克兰 lappa Decne. 胃肠道问题的根源;脱水乳 (DHL) 是一个关键组成部分.
- DHL对化疗诱导的肠粘膜炎的保护机制尚不清楚.
研究的目的:
- 为了研究脱水乳 (DHL) 对因虹膜素 (CPT-11) 诱导的肠粘膜炎的保护作用.
- 阐明潜在的分子机制,重点关注TLR4/NF-κB/NLRP3信号通路.
主要方法:
- 在CPT-11诱导的小鼠模型和LPS+CPT-11刺激的THP-1巨细胞中评估了DHL的保护作用.
- 在体内评估的参数:体重,腹得分,存活率,结肠长度和组织病理学.
- 研究了DHL对炎症性细胞因子和TLR4/NF-κB/NLRP3通路的影响,包括TLR4/MD2复合体的形成.
- 利用分子对接,SIP,DARTS测试和TLR4沉默 (siRNA) 来验证机制.
主要成果:
- DHL显著降低了CPT-11诱导的体重减轻,腹,死亡率和结肠缩短.
- 组织学分析显示,DHL可以预防肠上皮损伤,改善屏障功能.
- 在体内和体外,DHL通过抑制TLR4/NF-κB/NLRP3通路来降低炎症性细胞因子的调节.
- DHL阻断了TLR4/MD2复合体的形成,与MD2疏水口袋结合,这种效应取决于TLR4的表达.
- 在不影响CPT-11的抗瘤功效的情况下,DHL改善了肠道粘膜炎.
结论:
- 脱水乳 (DHL) 对CPT-11诱导的肠粘膜炎表现出显著的抗炎作用.
- DHL的功能是通过抑制TLR4/MD2复合体的形成,并随后调节NF-κB/NLRP3信号通路.
- DHL代表了与CPT-11联合使用的有希望的治疗策略,以减轻胃肠道毒性.
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