背景:睡眠不足,如表现为睡眠时间短或失眠症状,已知会增加涉及免疫病理学的多种疾病的风险。据推测,炎症是睡眠不足作为这些疾病的危险因素的一种机制。因此,减轻与睡眠不足相关的负面健康后果的一个潜在方法是靶向炎症。很少有干预性睡眠研究调查改善睡眠是否会影响炎症过程。但结果表明,补充方法可能需要针对与睡眠不足相关的炎症。我们调查了是否通过低剂量乙酰水杨酸靶向炎症(ASA,即,阿司匹林)能够减弱实验性睡眠限制的炎症反应。
方法:46名健康参与者(19F/27M,年龄范围19-63岁)在一项双盲随机安慰剂对照交叉试验中进行了研究,每个方案包括14天的家庭监测阶段,然后是11天(10晚)实验室停留(睡眠限制/ASA,睡眠限制/安慰剂,控制睡眠/安慰剂)。在睡眠限制/ASA条件下,参与者在家庭阶段和随后的实验室停留期间,在晚上(22:00)每日服用低剂量ASA(81mg/天).在睡眠限制/安慰剂和对照睡眠/安慰剂条件下,参与者每天服用安慰剂.每次实验室停留从2晚开始,睡眠机会为8小时/晚(23:00-07:00),用于适应和基线测量。在两种睡眠限制条件下,参与者暴露于5个晚上的睡眠,限制睡眠时间为4小时/夜(03:00-07:00),随后是3个晚上的恢复睡眠,睡眠时间为8小时/夜.在控制睡眠条件下,在整个实验室逗留期间,参与者的睡眠机会为8小时/晚.在每次实验室逗留期间,参与者进行了3天的强化监测(基线时,第5天睡眠限制/控制睡眠,和恢复睡眠的第二天)。变量,包括促炎免疫细胞功能,C反应蛋白(CRP),和活动图估计的睡眠测量,使用广义线性混合模型进行分析。
结果:低剂量ASA给药降低了LPS刺激的单核细胞中白细胞介素(IL)-6的表达(对于条件*天,p<0.05),并降低了血清CRP水平(对于条件为p<0.01)与睡眠限制条件下的安慰剂给药相比,在5个晚上的睡眠限制后。与安慰剂相比,低剂量ASA还减少了5晚睡眠限制后2晚恢复睡眠后LPS刺激的单核细胞中环氧合酶(COX)-1/COX-2双阳性细胞的量(p<0.05条件)。低剂量ASA在恢复睡眠的前2个晚上进一步降低了睡眠开始后的觉醒(WASO)并增加了睡眠效率(SE)(对于条件和条件*日,p<0.001)。基线比较显示所有研究变量的条件之间没有差异(条件p>0.05)。
结论:这项研究表明,预先给予低剂量ASA可以减少对睡眠限制的炎症反应。这一发现可能为预防或控制炎症及其在睡眠不足患者中的后果开辟了新的治疗方法。
背景:ClinicalTrials.govNCT03377543。
BACKGROUND: Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction.
METHODS: 46 healthy participants (19F/27M, age range 19-63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00-07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00-07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models.
RESULTS: Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition).
CONCLUSIONS: This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies.
BACKGROUND: ClinicalTrials.gov NCT03377543.