Purpose: To evaluate the correlation between sleep microstructure, autonomic nervous system activity, and neuropsychological characteristics in chronic insomnia (CI) patients with obstructive sleep apnea (OSA).Patients and Methods: Forty-five CI-OSA patients, forty-six CI patients and twenty-two matched healthy control subjects (HCs) were enrolled. CI-OSA patients were then divided into two groups: mild OSA and moderate-to-severe OSA. All participants completed neuropsychological tests, which included the Hamilton Depression and Anxiety Scales (HAMD and HAMA), the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), and the Mini-mental State Examination (MMSE). The autonomic nervous system activity and sleep microstructure were examined by the PSM-100A.Results: The CI-OSA patients exhibited higher scores on the PSQI, ESS, ISI, HAMA, and HAMD than HCs and CI patients (all p < 0.01). The CI-OSA patients had a lower proportion of stable sleep, REM sleep and a higher proportion of unstable sleep ratio (all p < 0.01) than HCs and CI patients (all p < 0.01). The CI-OSA patients had higher ratios of LF and LF/HF, and lower ratios of HF and Pnn50% (all p < 0.01) than HCs and CI patients (all p < 0.01). Compared to CI-mild OSA patients, the CI-moderate-to-severe OSA patients presented with a higher ESS scores, higher ratios of LF and LF/HF, and lower ratios of HF (all p < 0.05). In CI-OSA patients, higher HAMD scores were correlated with decreased MMSE scores (r=-0.678, p < 0.01). A higher LF ratio was correlated with higher HAMD and HAMA scores (r=0.321, p=0.031, r =0.449, p =0.002), and a higher HF ratio was correlated with lower HAMD and HAMA scores (r=-0.321, P =0.031, r =-0.449, p =0.002).Conclusion: OSA exacerbates the abnormalities of sleep microstructure and the autonomic nervous dysfunction in CI patients. Dysfunction of the autonomic nervous system could contribute to mood deterioration in CI with OSA patients.

目的 观察α7-nAChR/PI3K/AKT/GSK-3β通路在慢性睡眠剥夺后的保护作用,并探讨其作用机制.方法 成年C57BL/6J小鼠随机分为3组:对照(CC)组、慢性睡眠剥夺(SD)组、慢性睡眠剥夺后腹腔注射α7-nAChR激动剂-PHA-543613(SD+PHA-543613)组.采用Western-blot印迹检测各组小鼠海马组织α7-nAChR及p-AKT、p-GSK-3β、Nrf-2、HO-1蛋白表达变化;使用实时荧光定量PCR检测各组小鼠海马组织α7-nAChR mRNA水平及炎性因子与抑炎因子TNF-α、IL-1β、IFN-γ、MCP-1、Arg-1、CD206、TGF-β、YM-1mRNA表达水平;采用免疫荧光染色法观察各组小鼠海马组织星形胶质细胞、小胶质细胞表面α7-nAChR的表达变化;通过水迷宫评估小鼠的行为学.结果 慢性睡眠剥夺7 d后,SD组海马组织的α7-nAChR蛋白、mRNA的表达明显低于CC组(P=0.001,P=0.038),SD组海马组织p-AKT蛋白表达显著低于CC组(P=0.019),p-GSK-3β 蛋白表达量高于CC组(P=0.011);慢性睡眠剥夺后腹腔注射α7-nAChR激动剂-PHA-543613后海马组织星形胶质细胞表面α7-nAChR的表达高于SD组(P=0.027),p-AKT、p-GSK-3β 的蛋白表达也明显高于SD组(P=0.047,P=0.017);腹腔注射 α7-nAChR激动剂-PHA-543613后,SD+PHA-543613组海马组织Nrf-2、HO-1蛋白表达量和抑炎因子CD206、TGF-β的mRNA表达量与SD组相比明显增多(P=0.020,P=0.016,P<0.01,P<0.01),而促炎因子TNF-α、MCP-1的mR-NA表达量与SD组相比显著下降(均P<0.01).腹腔注射α7-nAChR激动剂-PHA-543613后小鼠的逃避潜伏期与SD组相比缩短,处于目标象限时间延长、穿越平台次数增多(P=0.000,P=0.000,P=0.001).结论 慢性睡眠剥夺后刺激α7-nAChR通过激活PI3K/AKT/GSK-3β减轻神经炎症和氧化应激.