时间：2025-07-25
最新研究揭示关键机制
泰国科研团队在《生理学报告》发表突破性研究，首次揭示维生素D不同形式在对抗血管紧张素II诱导的肌肉萎缩中的双刃剑效应。这项由清迈大学领衔的细胞实验研究，为慢性病患者肌肉萎缩的精准干预提供了全新视角。
研究聚焦肾素-血管紧张素系统过度激活引发的肌肉消耗问题，利用C2C12小鼠肌管细胞模型，模拟慢性病患者常见的病理状态。通过对比普通维生素D3（胆钙化醇）与其活性形式骨化三醇（1,25VD3）的作用差异，发现关键机制：
1.形态学保护差异：100nM维生素D3与降压药氯沙坦同样具有维持肌管直径的作用，而1-10nM骨化三醇反而激活MuRF1、atrogin-1等肌肉分解关键酶，提示活性维生素D可能加剧蛋白质分解。
2.自噬通路扰动：骨化三醇处理显著上调自噬标记物LC3B-II（增幅达2.3倍），同时降低p62/SQSTM1蛋白水平，揭示其通过异常激活自噬途径促进肌肉消耗。
3.氧化应激失衡：骨化三醇组出现活性氧簇（ROS）爆发性增长（较对照组升高58%），NADPH氧化酶-2过量产生，而超氧化物歧化酶和过氧化氢酶等抗氧化防御机制响应不足，形成恶性循环。
"这颠覆了我们对维生素D代谢物的传统认知。" 通讯作者Muthita Hirunsai博士指出，"研究证明维生素D3本身具有直接肌肉保护作用，而临床常用的活性形式骨化三醇在特定病理环境下可能产生负面效应。"
该研究首次系统阐明两种维生素D形式在肌肉萎缩中的相反作用，为慢性肾病、心衰等伴随血管紧张素系统激活的疾病治疗提供重要参考。专家建议，临床补充维生素D时应充分考虑患者病理状态，监测氧化应激指标，避免活性形式维生素D的潜在风险。
目前研究团队正着手开展动物实验，进一步验证不同维生素D形式的体内效应。此项发现或将推动维生素D制剂在肌肉萎缩防治中的精准应用，为全球约5亿慢性病患者改善肌肉健康提供新策略。研究获得泰国国家研究基金支持，所有作者声明无利益冲突。
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