前列腺素（PG）在睡眠调节中发挥着至关重要的作用，但导致前列腺素介导的睡眠促进系统激活的更广泛的生理背景仍然难以捉摸。在这项研究中，我们利用环氧合酶 2 敲除 (COX-2 KO) 小鼠及其野生小鼠，探索了可能涉及 PG 的睡眠诱导机制，包括微生物、免疫和热刺激，以及由短期睡眠剥夺诱导的稳态睡眠反应。同窝型（WT）。全身给予 0.4μg 脂多糖 (LPS) 会导致 WT 动物非快速眼动睡眠 (NREMS) 增加和发烧，而这些效应在 COX-2 KO 小鼠中完全不存在。这一发现强调了 COX-2 依赖性前列腺素在调节 LPS 的睡眠和发热反应中的重要作用。相比之下，由促炎细胞因子肿瘤坏死因子α（一种激活COX-2的促炎细胞因子）诱导的睡眠和发烧反应在COX-2 KO动物中得以保留，表明这些效应与COX-2相关发信号。此外，我们还研究了环境温度对睡眠的影响。 COX-2 KO 动物中中等温暖环境温度的睡眠促进作用受到抑制，导致与 WT 小鼠相比，在 30°C 和 35°C 环境温度下 NREMS 显着降低。然而，两种基因型之间对中等寒冷或温暖温度的快速眼动睡眠反应没有差异。此外，6 小时的睡眠剥夺会导致睡眠反弹增加，但 COX-2 KO 和 WT 小鼠之间没有观察到显着差异。这表明，虽然 COX-2 衍生的前列腺素对于环境温度升高的催眠作用至关重要，但对睡眠不足的稳态反应与 COX-2 无关。总体而言，结果强调了 COX-2 衍生的前列腺素作为睡眠觉醒和体温调节反应介质对各种生理挑战（包括微生物、免疫和热刺激）的关键作用。这些发现强调了体温和睡眠的相互调节，外围机制在这些综合过程中发挥着关键作用。版权所有 © 2024。由 Elsevier Inc. 出版。

Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by the pro-inflammatory cytokine tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes.Copyright © 2024. Published by Elsevier Inc.