不列颠哥伦比亚大学和威斯康星大学麦迪逊分校的研究人员利用冷冻电子显微镜技术，阐明了他汀类药物引发肌肉损伤的原理。1研究发现，他汀分子（以阿托伐他汀为例）会与肌肉细胞中的核糖体受体蛋白（RyR1）结合，其中三个他汀分子以特定方式进入该蛋白的通道口袋：第一个分子使通道更易打开，另两个分子随之锁定通道，使其保持在打开状态。1这种持续的打开导致钙离子不断泄漏到不应该存在的区域，最终引发肌肉疼痛和虚弱，严重情况下可能导致肌肉分解和肾衰竭。1
这项研究成果已发表在《自然通讯》期刊上，为开发更安全的他汀类药物提供了关键的科学依据。1全球超过2亿人使用他汀类药物，该发现有望帮助优化现有药物配方，减少患者的肌肉相关不良反应。1
Researchers from the University of British Columbia have identified the molecular basis for why statin drugs cause muscle pain, using cryo-electron microscopy to reveal the precise interactions between statin molecules and muscle cell proteins 1. The study, published in Nature Communications in 2025, found that statins such as atorvastatin bind to ryanodine receptor (RyR1) proteins—calcium channels in muscle cells—and force them to remain in an open position 1. This abnormal opening allows calcium ions to leak continuously into areas where they should not accumulate, disrupting normal muscle function 1.
The research demonstrated that three statin molecules attach to the calcium channel protein pocket in a coordinated manner: the first molecule makes the channel more prone to opening, while the other two lock it in the open state 1. Scientists from both the University of British Columbia and the University of Wisconsin-Madison collaborated on this research, which has significant implications given that over 200 million people worldwide use statins 1. The findings may guide the development of safer statin formulations, as this understanding of the drug's mechanism at the molecular level could help pharmaceutical researchers design alternatives that maintain the cardiovascular benefits of statins while minimizing muscle-related side effects 1. Statin-related muscle complications can range from pain and weakness to severe muscle breakdown and kidney failure in critical cases 1.
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