使用网络毒理学和分子动力学对斑马鱼中德克斯特罗梅索芬及其代谢物德克斯特罗索芬心脏毒性作用的机制性洞察
Zhou Cao1,2, Zhu Liang1,2, Jin-Ge Zhang1,2
1SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China.
Environmental science & technology
|January 30, 2026
概括
德克斯甲 (DXM) 和其代谢物德克斯甲 (DXO) 通过抑制β2-上腺素受体,损害斑马鱼的心脏功能. DXO表现出更强烈的心脏毒性,突出了对这些常见药物的生态风险评估的需要.
科学领域:
- 环境毒理学环境毒理学
- 心血管生理学心血管生理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 呼吸道疾病率的上升增加了抗咳药物的使用,导致制药污染物,如 dextromethorphan (DXM) 和其代谢物 dextrorphan (DXO) 在水生生态系统中.
- 关于DXM和DXO对鱼类的心脏毒性影响的研究有限,需要对它们对环境的影响进行调查.
研究的目的:
- 评估DXM和DXO对斑马鱼胚胎的心脏毒性影响.
- 通过网络毒理学和分子动力学阐明DXM和DXO诱导心脏毒性背后的分子机制.
主要方法:
- 斑马鱼胚胎在受精后72小时内暴露在不同度的DXM和DXO (100-10,000 ng/L) 中.
- 评估了心脏功能,形态测量和血液流动.
- 网络毒理学和分子动力学模拟用于识别分子标和结合相互作用.
主要成果:
- 暴露于DXM和DXO会导致心脏功能,形态学和血流的度依赖性抑制,包括胸.
- 确定β2-上腺素受体 (adrb2a) 是这两种化合物的关键分子标.
- 观察到adrb2a的下调,β2-上腺体受体和蛋白激酶A水平的降低,在与上腺素同时暴露时出现表型救援.
结论:
- DXM和DXO通过抑制β2-上腺素受体信号传递,从而损害斑马鱼心肌细胞功能,从而导致心.
- 德克斯托芬 (DXO) 的心脏毒性比德克斯托芬 (DXM) 的心脏毒性更大.
- 由于其强烈的心脏毒性作用,DXO的生态毒性需要进一步调查.
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