失眠症的中医证候分析与中药治疗概况

失眠症是指持续相当长时间的对睡眠的质和量不满意的状况,可引起精神无法集中、思考能力减退、警觉力与判断力下降、免疫功能低下、内分泌紊乱等,还与感冒、抑郁症、糖尿病、肥胖、中风、心脏病和癌症的发生有关。现代社会,随着生活水平的提高,体力劳动减少,脑力劳动增加,工作及精神压力日益加重,很多失眠患者情志不畅的表现尤为突出。经过临床观察,我们发现五脏气机失调在失眠症的辨证论治中占有主导作用,因此对失眠及失眠症的研究与治疗就成为重要课题。     

AMBER LENSES TO BLOCK BLUE LIGHT AND IMPROVE SLEEP: A RANDOMIZED TRIAL

All light is not equal: blue wavelengths are the most potent portion of the visible electromagnetic spectrum for circadian regulation. Therefore, blocking blue light could create a form of physiologic darkness. Because the timing and quantity of light and darkness both affect sleep, evening use of amber lenses to block blue light might affect sleep quality. Mood is also affected by light and sleep; therefore, mood might be affected by blue light blockade. In this study, 20 adult volunteers were randomized to wear either blue-blocking (amber) or yellow-tinted (blocking ultraviolet only) safety glasses for 3?h prior to sleep. Participants completed sleep diaries during a one-week baseline assessment and two weeks' use of glasses. Outcome measures were subjective: change in overall sleep quality and positive/negative affect. Results demonstrated that sleep quality at study outset was poorer in the amber lens than the control group. Two- by three-way ANOVA revealed significant (p?<?.001) interaction between quality of sleep over the three weeks and experimental condition. At the end of the study, the amber lens group experienced significant (p?<?.001) improvement in sleep quality relative to the control group and positive affect (p?=?.005). Mood also improved significantly relative to controls. A replication with more detailed data on the subjects' circadian baseline and objective outcome measures is warranted. (Author correspondence: jphelps@samhealth.org)     

Is daily routine important for sleep? An investigation of social rhythms in a clinical insomnia population

Social rhythms, also known as daily routines (e.g. exercise, of school or work, recreation, social activities), have been identified as potential time cues to help to regulate the biological clock. Past research has shown links between regularity and healthy sleep. This study examined the regularity and frequency of daytime activities in a clinical insomnia population and a good sleeper comparison group. Participants (N?=?69) prospectively monitored their sleep and daily activities for a 2-week period. Although participants with insomnia and good sleepers had similar levels of activity, relative to good sleepers, those with insomnia were less regular in their activities. Findings from this study add to the growing number of studies that highlight the relative importance of the regularity of daytime activities on sleep. Accordingly, future research should test treatment components that focus on regulating daytime activities, which would likely improve treatment outcomes.     

荧光高效液相色谱法测定三种失眠模型大鼠脑组织氨基酸类神经递质的含量

目的测定睡眠剥夺大鼠脑组织氨基酸类神经递质的含量。方法复制药物诱导失眠动物模型、平台水环境诱导失眠动物模型、刺激诱导失眠动物模型,以Agilent 1100荧光检测器高效液相系统为检测工具,Agilent ZORBAX SB-Aq(250 mm×4.6 mm,5μm)为色谱柱,柱温25℃,激发波长λex=357 nm,发射波长λem=455 nm,甲醇-50 mmoL/L醋酸钠缓冲液(pH=6.5)为流动相,采取梯度洗脱,测定正常组及模型组大鼠脑组织中谷氨酸(Glu)、甘氨酸(Gly)、γ-氨基丁酸(γ-GABA)、牛磺酸(Tau)的含量。结果谷氨酸、甘氨酸、γ-氨基丁酸、牛磺酸分别在10.06～0.0503、10.13～0.0506、10.05～0.0502、10.03～0.0501μg/mL范围内,其浓度与峰面积呈良好的线性关系(r分别为0.99995、0.99995、0.99985、0.99990)。测得药物诱导失眠大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.2042±0.0145)、(0.0086±0.0005)、(0.0919±0.0024)、(0.0421±0.0011)μg;平台水环境诱导失眠大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.2144±0.0159)、(0.0085±0.0004)、(0.0966±0.0035)、(0.0433±0.0012)μg;刺激诱导失眠大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.1818±0.0043)、(0.0084±0.0005)、(0.0824±0.0033)、(0.0414±0.0018)μg;正常大鼠脑组织中Glu、Gly、Tau、γ-GABA的含量为(0.1744±0.0038)、(0.0085±0.0004)、(0.0791±0.0022)、(0.0406±0.0012)μg。结论本实验建立的方法能满足同时测定大鼠脑组织中谷氨酸、甘氨酸、γ-氨基丁酸、牛磺酸的含量测定的需要,Glu、Tau、γ-GABA与失眠可能存在一定的量效关系,三种失眠动物模型均能较好的反映出脑内氨基酸类神经递质的变化。     

The assessment and management of insomnia: an update

Insomnia poses significant challenges to public health. It is a common condition associated with marked impairment in function and quality of life, psychiatric and physical morbidity, and accidents. As such, it is important that effective treatment is provided in clinical practice. To this end, this paper reviews critical aspects of the assessment of insomnia and the available treatment options. These options include both non‐medication treatments, most notably cognitive behavioral therapy for insomnia, and a variety of pharmacologic therapies such as benzodiazepines, “z‐drugs”, melatonin receptor agonists, selective histamine H1 antagonists, orexin antagonists, antidepressants, antipsychotics, anticonvulsants, and non‐selective antihistamines. A review of the available research indicates that rigorous double‐blind, randomized, controlled trials are lacking for some of the most commonly administered insomnia therapies. However, there are an array of interventions which have been demonstrated to have therapeutic effects in insomnia in trials with the above features, and whose risk/benefit profiles have been well characterized. These interventions can form the basis for systematic, evidence‐based treatment of insomnia in clinical practice. We review this evidence base and highlight areas where more studies are needed, with the aim of providing a resource for improving the clinical management of the many patients with insomnia.     

益气安神膏对心脾两虚型失眠患者睡眠质量及中医证候疗效的影响

目的:观察益气安神膏对心脾两虚型失眠患者睡眠质量及中医症候疗效的影响,为膏方应用于失眠调理提供理论依据。方法:选取2016年10月至2017年10月来广州中医药大学第一附属医院就诊的70例心脾两虚型失眠患者作为研究对象,按照就诊顺序,由电脑产生随机数字,根据数字奇偶性分为对照组(35例)和试验组(35例)。在认知行为治疗(CBT-I)干预基础上,试验组予口服益气安神膏1匙(约15g)/次,每日2次,对照组予口服归脾丸10丸/次,每日3次,4周为1疗程,两组均连续服用8周2疗程。采用匹兹堡睡眠质量指数量表(PSQI)、中医证候评分量表评分评估睡眠质量及中医证候疗效。结果:试验组总有效率为94.3%(治愈2例,有效31例),高于对照组的77.1%(治愈1例,有效26例),差异有统计学意义(P0.05)。治疗前,两组PSQI评分差异无统计学意义(P0.05);治疗后,试验组得分(8.1±2.8)分,对照组得分(10.4±3.8)分,前者明显低于后者,差异具有统计学意义(P0.05)。中医证候疗效方面,相较于对照组,试验组疗效更佳,差异有统计学意义(P0.05)。结论:益气安神膏在改善睡眠质量及中医证候疗效方面均优于归脾丸,其临床疗效明显,服用方便,可适用于临床慢性失眠患者的调理。     

GABA 能系统与失眠

γ-氨基丁酸(GABA)是一种重要的抑制性神经递质,众多研究表明,GABA能系统功能异常与失眠以及焦虑,抑郁等情感障碍关系密切。焦虑,抑郁等神经心理异常可能是引发失眠的原因之一。本文总结了GABA能系统与失眠及情感障碍关系,为治疗失眠提供新的理论依据。     

基于心脾同治理论观察扶正养心汤对焦虑性失眠患者的临床疗效

摘要 目的：观察扶正养心汤治疗心脾两虚型焦虑性失眠患者的临床疗效,探索扶正养心汤治疗心脾两虚型焦虑性失眠的可能性机制。方法：在中医情志病门诊就诊患者中,选取的心脾两虚型焦虑性失眠患者50例,按照随机数表法分为观察组和对照组各25例,对照组给予艾司唑仑片,1 mg,1次/d,观察组在对照上基础上加服扶正养心汤,2次/d,共14天,分别在治疗前后,比较两组患者WBC、IL-6、IgA表达水平以及生活质量评分（SF-36）、匹兹堡睡眠质量量表（PSQI）评分、焦虑自测量表（SAS）评分、中医证候积分及治疗后总有效率。结果：治疗后,组内相比,两组患者WBC、IL-6、IgA表达水平均较前下降（P＜0.05）,两组患者PSQI评分、SAS评分均较治疗前降低（P＜0.05）,SF-36评分较前升高（P＜0.05）,观察组中医证候积分降低（P＜0.05）,对照组中医证候积分降低无统计学差异（P＞0.05）;组间相比,观察组WBC、IL-6、IgA较对照组降低更明显（P＜0.05）,SF-36较对照组提升更为明显（P＜0.05）,PSQI评分和SAS评分降低更明显（P＜0.05）,且总有效率更高（P＜0.05）。结论：扶正养心汤可改善心脾两虚型焦虑性失眠患者睡眠质量、临床症状和生活质量;相较于单纯使用艾司唑仑,疗效更佳。可能与扶正养心汤可降低患者WBC、IL-6、IgA水平相关。     

Discovery of MK-3697: A selective orexin 2 receptor antagonist (2-SORA) for the treatment of insomnia

Orexin receptor antagonists have demonstrated clinical utility for the treatment of insomnia. The majority of clinical efforts to date have focused on the development of dual orexin receptor antagonists (DORAs), small molecules that antagonize both the orexin 1 and orexin 2 receptors. Our group has recently disclosed medicinal chemistry efforts to identify highly potent, orally bioavailable selective orexin 2 receptor antagonists (2-SORAs) that possess acceptable profiles for clinical development. Herein we report additional SAR studies within the ‘triaryl’ amide 2-SORA series focused on improvements in compound stability in acidic media and time-dependent inhibition of CYP3A4. These studies resulted in the discovery of 2,5-disubstituted isonicotinamide 2-SORAs such as compound 24 that demonstrated improved stability and TDI profiles as well as excellent sleep efficacy across species.