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鲁斯科根因通过ErbB4/YAP和ROCK/MLC通路改善了达沙替尼诱导的肠壁功能障碍
Juan Huang1, Jianhao Zhou1, Yujie Dai1
1Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Pharmacology of Chinese Materia Medica, School of Traditional Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, People's Republic of China.
Journal of natural medicines
|June 22, 2023
概括
鲁斯科根因 (RUS) 通过保持血液流动和增强内皮细胞连接,保护免受达沙提尼布诱导的肠壁功能障碍. 它调节关键信号通路,为达沙替尼的副作用提供了潜在的治疗策略.
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
- 细胞生物学 细胞生物学
背景情况:
- 用于白血病的达沙替尼可以引起胃肠道出血.
- 来自传统中医药的鲁斯科根因 (RUS) 可能会保护内皮壁垒.
研究的目的:
- 为了研究RUS对达沙提尼布诱导的肠壁功能障碍的治疗作用.
- 阐明RUS干预的潜在分子机制.
主要方法:
- 在体内研究中,使用大沙替尼和RUS治疗的小鼠.
- 使用暴露于达沙替尼和RUS.的人类静脉内皮细胞 (HUVEC) 的体外研究.
- 对肠道血液流动,透性标记物 (埃文斯蓝色,FITC-dextran) 和蛋白质表达 (ErbB4,YAP,ROCK,MLC,ZO-1,Occludin,VE-cadherin) 的分析.
主要成果:
- 达沙替尼减少了肠道血液流动和障碍屏障功能.
- RUS增加了肠道血液流动,减少了泄漏,并改善了屏障完整性.
- 在体外和体外模型中,RUS调节了ErbB4/YAP和ROCK/MLC信号通路.
结论:
- RUS有效地减轻了达沙替尼诱导的肠壁功能障碍.
- RUS通过调节ErbB4/YAP和ROCK/MLC通路而起作用.
- RUS显示出作为防护剂的潜力,可以防止达沙替尼的胃肠道副作用.
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