失眠的发病率逐年升高，亟需开发具有改善睡眠功效的活性物。该研究利用秀丽隐杆线虫（Caenorhabditis elegans）从α-乳白蛋白、γ-氨基丁酸、L-茶氨酸和百合提取物四种活性物中筛选出改善睡眠效果最佳的物质并探究其改善睡眠的机制，最后将其开发成具有改善睡眠功效的复合组合物。结果表明，四种活性物均能降低与线虫睡眠相关的活性氧水平，且α-乳白蛋白改善线虫与睡眠相关的氧化应激效果最佳。经α-乳白蛋白干预后，线虫线粒体损伤减少了65.00%（P<0.05），并且应激胁迫下线虫最大寿命显著延长了4.10%（P<0.05）。最后，含α-乳白蛋白复合组合物促睡眠效果最佳的配方不仅能将线虫发育阶段睡眠的睡眠时长和睡眠频率分别提高7.97%（P<0.05）和59.43%（P<0.05），还能显著降低线虫应激诱导睡眠的运动速率。综上所述，四种活性物中，改善线虫睡眠相关氧化应激效果最佳的是α-乳白蛋白并且其改善睡眠的机制与线粒体修复有关，含α-乳白蛋白复合组合物具有改善线虫睡眠的作用。

With the incidence of insomnia increasing each year, there is an urgent need to develop active substances that can improve sleep. Caenorhabditis elegans was used to screen substances with the best sleep-improving effect from among four natural active substances (α-lactalbumin, γ-aminobutyric acid, L-theanine, and lily extract), and the mechanisms underlying their sleep-improving effects were examined. Finally, composites with sleep-improving effects were developed using these active substances. The results showed that all four natural active substances could reduce the levels of sleeprelated reactive oxygen species in C. elegans, and that α-lactalbumin had the best effect on improving sleep-related oxidative stress. Caenorhabditis elegans subjected to α-lactalbumin administration showed a 65.00% reduction in mitochondrial damage (P<0.05) and 4.10% increase in maximum lifespan under Pseudomonas aeruginosa PAO1 stress (P<0.05). Finally, the α-lactalbumin-containing composite with the best sleep-improving effect significantly increased sleep duration by 7.97% (P<0.05) and sleep frequency by 59.43% (P<0.05) during developmentally timed sleep, and reduced the movement speed of stress-induced sleep in C. elegans. In conclusion, α-lactalbumin had the strongest effect among the four active substances tested on improving sleep-related oxidative stress in C. elegans, and the mechanism of improving C. elegans sleep was related to mitochondrial repair. Composites containing α-lactalbumin showed sleep-improving effects in C. elegans.

广东省自然科学基金面上项目（2023A1515011266）