慢性多药,单药和减药:了解老年小鼠肝脏蛋白质组的复杂影响
Kevin Winardi1, John Mach1, Matthew J McKay2
1Laboratory of Ageing and Pharmacology, Kolling Institute, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, Sydney, New South Wales, Australia.
Aging cell
|October 28, 2024
概括
在老年人中,多种药物会导致肝脏发生重大变化,影响免疫力和新陈代谢. 处方可以扭转一些影响,但也会引起新的影响,为老年人管理多种药物提供了洞察力.
科学领域:
- 老年学是一门学科.
- 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:
- 多药性 (≥5种药物) 在老年人中很常见,增加功能衰退,跌倒,住院和死亡的风险.
- 停止处方 (停药) 是一种减轻多药药的不良影响的策略.
- 多药药的危害和抑郁药的益处背后的分子机制在很大程度上是未知的.
研究的目的:
- 在老年小鼠中研究与慢性多药和随后的抑郁相关的肝脏分子变化.
- 为了比较单疗法与多疗法对肝脏蛋白质的作用.
- 确定将药物效应与老年患者的结果联系起来的分子通路.
主要方法:
- 雄性C57BL/6J小鼠从中年到老年接受了常见的慢性药物,作为单疗法或多疗法.
- 一组小鼠从21个月大开始接受了抑郁症.
- 肝脏蛋白质组学,转录组学和组织学被用来分析与药物相关的影响.
主要成果:
- 多药学诱导了肝脏蛋白质的显著变化 (93%是多药学独有的),改变了免疫力和药物,胆固醇和氨基酸代谢.
- 与多药疗法相比,单一疗法对肝脏蛋白质的作用有限.
- 降低处方可以扭转一些多药物诱导的变化,但也引入了肝脏蛋白质组中不可逆转的新变化.
- 特定的肝蛋白模块与老年期的结果相关,如移动性和脆弱性.
结论:
- 慢性多药在衰老中显著改变肝脏的分子通路,影响新陈代谢和免疫力.
- 处方开始复杂的分子反应,包括逆转和肝脏的新变化.
- 这些发现提供了对多药房的影响和减药的潜在好处的机制性见解,为老年人提供了临床管理策略的信息.
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