乙胆化酶抑制通过减少多种编程细胞死亡途径,保护免受trastuzumab诱导的心脏毒性
Thawatchai Khuanjing1,2,3, Chayodom Maneechote1,3, Benjamin Ongnok1,2,3
1Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Molecular medicine (Cambridge, Mass.)
|September 10, 2023
概括
多尼佩西尔通过减少炎症,氧化应激和细胞死亡,从而改善心脏功能来保护特拉斯图祖马布诱导的心脏毒性 (TIC). 这表明donepezil是TIC的潜在新疗法.
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
背景情况:
- 特拉斯图祖马布诱导的心脏毒性 (TIC) 是癌症治疗的常见副作用.
- TIC的机制包括氧化应激,炎症和细胞死亡,但热和死的作用尚未被探索.
- 多尼西尔在心脏病中表现出保护作用,但其在TIC中的疗效尚不清楚.
研究的目的:
- 在大鼠模型中研究多尼佩西尔对Trastuzumab诱导的心脏毒性的潜在心脏保护作用.
- 为了确定多尼佩西尔是否减轻线粒体功能障碍,炎症,氧化应激和TIC中的心肌细胞死亡.
- 探索肌肉酸乙胆受体 (mAChRs) 在多尼佩西尔心脏保护作用中的作用.
主要方法:
- 雄性Wistar大鼠被分为控制,Trastuzumab (Trz) 和Trz + Donepezil (DPZ) 组.
- Trz是以4mg/kg/天7天的剂量给予的;DPZ是以5mg/kg/天的同时给予的.
- 评估了心脏功能,心率变化 (HRV) 和生化标志物. 在体外研究中使用了肌肉酸乙胆受体 (mAChR) 抗剂.
主要成果:
- 特拉斯图祖马布治疗损害了左心室 (LV) 功能,HRV和线粒体功能,同时增加了炎症,氧化应激,亡,铁亡和热亡.
- 多尼尼西尔的联合治疗显著改善了LV功能和HRV,并减轻了TIC的不良影响.
- 在体外,多尼佩西尔的细胞保护作用被mAChR抗剂阻断.
结论:
- 多尼佩西尔显示出显著的心脏保护作用,可以预防Trastuzumab诱导的心脏毒性.
- 通过减少线粒体功能障碍,氧化应激,炎症和心肌细胞死亡来实现心脏保护.
- 多尼佩西尔的作用通过mAChR激活进行介导,这表明其作为TIC的新治疗策略的潜力.
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