快速眼动睡眠剥夺对抑郁模型大鼠纹状体5-HTDA及腺苷的影响

目的：通过对抑郁模型大鼠的快速眼动睡眠剥夺,观察大鼠强迫游泳不动时间及大鼠纹状体5-羟色胺、多巴胺和腺苷水平的变化,了解睡眠剥夺快速改善抑郁情绪的可能机制。方法将30只成年健康雄性大鼠分为正常对照组（A组）、抑郁模型组（B组）、抑郁模型＋睡眠剥夺组（C组）,在建立慢性轻度不可预见性应激的抑郁模型后,采用小平台水环境法对大鼠进行72 h快速眼动睡眠剥夺,以强迫游泳实验检测大鼠的不动时间,采用高效液相色谱-荧光检测法测定3组大鼠纹状体5-羟色胺、多巴胺水平,采用高效液相色谱-紫外检测法测定3组大鼠纹状体腺苷水平。结果21 d慢性轻度不可预见性应激后,大鼠的强迫游泳不动时间显著延长（ P＜0．05）,快眼动睡眠剥夺后大鼠强迫游泳不动时间显著缩短（P＜0．01）。A组、C组大鼠纹状体5-羟色胺及腺苷水平均显著高于B组（ P＜0．05或0．01）,C组大鼠纹状体多巴胺水平显著高于A组、B组（P＜0．01）。结论快速眼动睡眠剥夺可以逆转大鼠的抑郁样行为,并提高大鼠纹状体5-羟色胺、多巴胺水平,腺苷可能参与了睡眠剥夺的抗抑郁过程。     

金丝桃素对抑郁大鼠行为及脑内5-羟色胺和去甲肾上腺素表达的影响

目的：研究贯叶连翘提取物对抑郁大鼠行为学及脑内5-羟色胺、去甲肾上腺素(noradrenaline，NA)表达的影响。方法：选用雄性Wistar大鼠72只。制作大鼠慢性应激抑郁模型，应用敞箱法、跳台法、免疫组织化学染色研究贯叶连翘提取物对抑郁大鼠行为学、脑病理学的影响。结果：慢性应激抑郁大鼠的走格数与站立数显著少于对照组(P&;lt;0.01)，贯叶连翘提取物150．0，75．Omg／kg组大鼠走格数与站立数明显多于模型组(P&;lt;0．05，P&;lt;0．01)；贯叶连翘提取物37．5mg／kg组大鼠走格数(27&;#177;14)明显多于模型组(18&;#177;5)(P&;lt;0．05).慢性应激抑郁大鼠跳台行为学出现明显变化，表现为逃避反应的获得欠缺而停留期显著延长(P&;lt;0．05)，贯叶连翘提取物150.0，75．0mg／kg组大鼠错误反应的停留期明显少于模型大鼠(P&;lt;0．05).5-羟色胺、NA在贯叶连翘提取物150．0，75.0mg／kg组大鼠脑内的表达明显强于模型组(P&;lt;0．01)。结论：贯叶连翘提取物通过增强抑郁大鼠脑内5-羟色胺、NA表达，改善抑郁症状．     

产后抑郁患者血清P,E2,5-HT,NE和E水平在不同护理方法干预后的变化

目的 研究以家庭为中心的产科优质护理对产后抑郁患者血清孕酮(P)、雌二醇(E2)、5-羟色胺(5-HT)、去甲肾上腺素(NE)和肾上腺素(E)水平的影响。方法 选择2016年1月～2017年12月宝鸡市人民医院收治的92例产后抑郁患者,随机分为两组。对照组采用常规的抑郁症护理方法,观察组采用以家庭为中心的产科优质护理方案。比较两组的血清P,E2,5-HT,NE和E水平。结果 两组护理后的血清P,NE和E水平均明显降低,血清E2和5-HT水平均明显升高,差异均有统计学意义(t值分别为2.57,8.34,2.46,4.75,2.38; 7.92,11.26,3.49,6.27,3.52,均P<0.05),且观察组明显优于对照组,差异有统计学意义(t值分别为4.27,5.14,3.98,4.76,5.92,均P<0.05); 两组护理后SDS评分和SAS评分均明显降低,差异有统计学意义(t值分别为2.43,7.92; 5.34,8.21,均P<0.05),且观察组更为明显,差异有统计学意义(t值分别为3.78,4.12,均P<0.05); 观察组的有效率明显高于对照组,差异具有统计学意义(χ²=4.42,P<0.05)。结论 以家庭为中心的产科优质护理可以有效缓解产后抑郁患者的症状,改善其血清P,E2,5-HT,NE和E水平,值得应用推广。     

快眼动睡眠指标对抑郁障碍临床诊断的意义

目的探索快眼动(rapid eye movements,REM)睡眠的一些指标改变在抑郁障碍诊断中的意义.方法采用ICD-10作为临床诊断标准,以REM睡眠9项指标的改变作为判定抑郁障碍的电生理标准,分别对120例门诊和住院的精神疾病患者进行筛查,并通过计算Kappa值对两种诊断方式的一致性进行评估.结果120例患者中,通过临床诊断确诊抑郁障碍患者52例,以REM睡眠潜伏期缩短、REM活动度、REM强度、REM密度以及REM睡眠次数增加等改变甄别出的抑郁障碍患者59例,两种诊断方式具有较好的一致性(Kappa值为0.73,P＜0.05).结论REM睡眠上述指标的联合改变,对抑郁障碍的诊断有一定的意义,值得关注和进一步研究.     

快速眼动期睡眠剥夺对大鼠学习记忆和海马NR2B含量的影响

目的观察快速眼动期（ rapid eye movement ,REM）睡眠剥夺对大鼠空间学习记忆能力以及海马N-甲基-D-天冬氨酸（ N-methyl-D-aspartic acid receptor ,NMDA）受体亚基NR2B表达的变化,探讨睡眠剥夺影响认知功能的可能机制。方法20只成年健康雄性SD大鼠随机分为两组：（1）睡眠剥夺组（n＝10）;（2）普通鼠笼对照组（ n＝10）。睡眠剥夺组采用改良多平台睡眠剥夺法剥夺大鼠快速眼动期睡眠,连续72 h快速眼动期睡眠剥夺后,利用Morris水迷宫测定大鼠空间学习记忆能力,Western blot方法检测大鼠海马NR2B亚型的表达。结果 Morris水迷宫定位航行实验中,睡眠剥夺组大鼠找到月台的平均逃避潜伏期明显大于对照组;空间探索实验中睡眠剥夺组大鼠在月台所在象限时间的百分比为（26.84±4.99）％,明显低于对照组[（44.31±7.48）％,P＜0.05]。睡眠剥夺组大鼠海马NR2B的相对含量为0.46±0.14,而对照组为0.96±0.32（P＜0.01）。结论睡眠剥夺可导致大鼠的空间学习记忆能力降低,其机制可能与海马NR2B表达减少有关。     

快速眼动睡眠行为障碍对帕金森病患者认知功能的影响

目的分析快速眼动睡眠行为障碍(RBD)与帕金森病(PD)的相关性以明确RBD对PD患者认知功能的影响。方法回顾性分析123例PD患者的临床资料,根据是否伴有RBD将患者分为PD+RBD组(67例)和PD-RBD组(56例),比较2组各项资料的差异。采用Spearman秩相关分析检验多导睡眠监测睡眠参数与神经心理学相关指标的关系。结果 PD+RBD组病程长于PD-RBD组,总睡眠时间短于PD-RBD组,R期周期性腿动指数高于PD-RBD组(P均<0.05)。PD+RBD组蒙特利尔认知评估量表(MoCA)总分低于PD-RBD组,差异主要表现在执行能力、延迟记忆、注意力及抽象能力方面(P均<0.05)。PD+RBD组Stroop色词测验完成时间和错误数长/多于PD-RBD组(P均<0.05)。PD患者总睡眠时间和睡眠效率与MoCA总分、执行能力及注意力呈正相关,而与Stroop色词测验完成时间及错误数呈负相关(P均<0.05)。结论RBD可能是PD患者认知功能障碍特别是执行功能障碍的重要危险因素。     

脑卒中后抑郁模型大鼠脑单胺递质变化及中药颐脑解郁方的干预作用

目的：观察脑卒中后抑郁模型大鼠脑内单胺神经递质水平变化，以及中药颐脑解郁方对其的影响。方法：实验于2004-01-15／05在北京中医药大学基础医学院科研中心实验室及中心实验室高效液相测试中心进行。取雄性Wistar大鼠60只，随机分为正常组、脑卒中组、模型组、氟西汀组、颐脑解郁方组，每组12只。正常组不干预，其他4组复制局灶脑缺血模型，除脑卒中组外复制大鼠脑卒中后抑郁模型。造模结束后第1天分别开始灌胃双蒸水、氟西汀、颐脑解郁方共6周。用高效液相-电化学法测定脑前皮质、海马去甲。肾上腺素、多巴胺、5-羟色胺及其代谢物5-羟基吲哚乙酸含量。结果：60只大鼠全部进入结果分析。在大脑前皮质中：①5-羟色胺含量：正常组[(512．78&;#177;73．00)ng／g]及脑卒中组[(484．05&;#177;55．92)ng／g]高于模型组[(375．93&;#177;86．35)ng／g]，氟西汀组[(465．04&;#177;86．85)ng／g]和颐脑解郁方组[(459．41&;#177;68．24)ng／g]较模型组显著增加，但此两组间无差异。②去甲肾上腺素含量：模型组[(368．59&;#177;84．24)ng／g]较正常组显著降低[(438．82&;#177;63．21)ng／g]，颐脑解郁方组[(485．9l&;#177;58．98)ng／g]较模型组显著增加。③5-羟基吲哚乙酸含量：正常组[(615．68&;#177;65．01)ng／g]及脑卒中组[(600．67&;#177;41．17)ng／g]高于模型组[(501．78&;#177;82．88)ng／g]，氟西汀组[(590．05&;#177;86．45)ng／g]较模型组显著增加(P&;lt;0．05)。在脑海马组织中：①5-羟色胺含量：模型组[(167．97&;#177;36．71)ng／g]较正常组[(351．46&;#177;69．23)ng／g]和脑卒中组[(325．94&;#177;68．17)ng／g]显著降低，氟西汀组[(375.64&;#177;97．79)ng／g]和颐脑解郁方组[(248．73&;#177;58．99)ng／g]较模型组显著增加。②多巴胺含量：模型组[(18．49&;#177;5．17)ng／g]较正常组[(25．33&;#177;6．91)ng／g]显著降低，颐脑解郁方组[(27．94&;#177;7．22)ng／g]较模型组显著增加(P&;lt;0．01)。③去甲。肾上腺素含量：模型组[(368．62&;#177;51．48)ng／g]较正常组[(664．88&;#177;62．63)ng／g]显著降低，颐脑解郁方组[(428．52&;#177;39．24)ng／g]较模型组显著增加(P&;lt;0．05)。结论：脑卒中后抑郁大鼠存在脑单胺神经递质含量的减少，中药颐脑解郁方可增加其中枢5-羟色胺去甲。肾上腺素、多巴胺含量。     

阿戈美拉汀治疗抑郁症临床疗效及对患者血清5-HT NE水平的影响

目的 探讨阿戈美拉汀治疗抑郁症的临床疗效及对患者血清5-羟色胺、去甲肾上腺素水平的影响.方法 将65例抑郁症患者按照随机数字表法分为阿戈美拉汀组32例,帕罗西汀组33例,分别口服阿戈美拉汀、帕罗西汀治疗,观察16周.治疗前后采用汉密顿焦虑量表、汉密顿抑郁量表评定焦虑、抑郁状况,采用匹兹堡睡眠质量指数量表评定睡眠质量,检...     

REM睡眠剥夺对小鼠海马tau蛋白磷酸化的影响

目的探讨快速眼球运动(REM)睡眠剥夺(SD)对小鼠海马tau蛋白磷酸化的影响。方法将32只雄性昆明小鼠随机分为对照组、REMSD 24 h、REMSD 48 h及REMSD 72 h组。采用伊红染色(HE)法观察小鼠海马形态结构变化,利用免疫组化法观察磷酸化tau蛋白(p-tau)及总tau蛋白(T-tau)表达的变化。结果 REMSD 24 h组海马神经元结构即发生改变,出现细胞间隙增宽,排列欠整齐,但水肿不明显,REMSD 72 h组神经元损伤较明显,细胞排列疏松,部分神经元胞浆减少、细胞核出现固缩呈浓染,染色质颗粒欠清晰。免疫组化结果显示,对照组、REMSD 24 h、48 h及72 h组小鼠海马p-tau平均光密度分别为0.104 0.007、0.156 0.027、0.180 0.030和0.188 0.032(P0.05),REMSD各组均高于对照组,差异有统计学意义。无论对照组或是REMSD组,T-tau平均OD值均无显著差异。结论 REMSD可以引起小鼠海马p-tau增加,而不引起T-tau的改变。     

REM睡眠剥夺对大鼠焦虑行为的影响及瘦素的作用

目的:研究REM睡眠剥夺对大鼠焦虑行为的影响及瘦素的作用.方法:成年雄性Wistar大鼠90只随机分为9组(n=10),分别为生理盐水群居对照(NS)24 h、72 h、120 h组;生理盐水REM睡眠剥夺(NS-SD)24 h、72 h、120 h组和瘦素REM睡眠剥夺(L-SD)24 h、72 h、120 h组.均为腹腔注射给药.大鼠的REM睡眠剥夺模型采用小平台水环境法建立,大鼠的焦虑行为采用高架十字迷宫(elevated plus-maze,EPM)测试,分别观察瘦素和生理盐水对REM睡眠剥夺(SD)大鼠(第24、72、120小时)焦虑行为的影响.结果:成功建立REM睡眠剥夺模型及高架十字迷宫焦虑模型.大鼠焦虑行为结果:(1)与NS组相比,NS-SD组在24 h(F=5.32,P=0.01)和120 h(F=15.06,P=0.00)时EPM的总次数增加,L-SD组在120 h时的总次数降低;(2)NS-SD组在120 h时的开臂次数%(χ2=21.55,P=0.00)和开臂时间%(χ2=22.53,P=0.00)均显著增加,L-SD组在120 h时的开臂次数%和开臂时间%显著减少.结论:REM睡眠剥夺与大鼠焦虑行为的变化呈时间相关性,瘦素可减少长期REM睡眠剥夺导致的大鼠焦虑行为.因此,瘦素可能参与了REM睡眠剥夺的抗焦虑作用.     

Effects of 72 hours sleep deprivation on wound healing in the rat

The purpose of this study was to examine effects of sleep deprivation on cellular and biochemical markers of wound healing. Expanded polytetrafluoroethylene tubing inserted in subcutaneous tissue created miniature wounds in the dorsal skin of 12 rats. Seven days later, 6 rats were deprived of sleep by the platform method for 72 hr; control rats remained on usual sleep/wake routines. Numbers of macrophages, granulocytes, fibroblasts, and extent of connective tissue present and total amounts of protein, DNA, and hydroxyproline in the implants were not different between sleep-deprived and control rats. There is no evidence from this study that sleep deprivation impairs cellular and biochemical indicators of tissue repair. © 1997 John Wiley & Sons, Inc. Res Nurs Health 20: 259–267, 1997     

The effects of total and REM sleep deprivation on laser-evoked potential threshold and pain perception

We investigated the effects of total and rapid eye movement (REM) sleep deprivation on the thermal nociceptive threshold and pain perception using the objective laser-evoked potential (LEP) and the subjective visual analogue scale (VAS). Twenty-eight male adult volunteers were assigned into Control (CTRL), Total (T-SD), and REM (REM-SD) Sleep Deprivation groups. The T-SD and REM-SD volunteers were totally or selectively deprived of sleep for 2 and 4 consecutive nights, respectively. Pain parameters were measured daily during the experimental period. Volunteers were stimulated on the back of the hand by blocks of 50 diode laser pulses. Intensities increased between successive blocks, ranging from nonnoxious to noxious levels, and the LEP threshold was identified based on the evoked-response onset. Both the LEP threshold and VAS ratings were significantly increased after the second night of T-SD. No significant variations were observed in the REM-SD group, suggesting a predominant role for slow wave sleep rather than selective REM-SD in pain perception. Also, for both sleep-deprived groups, the mean values of the LEP threshold and VAS ratings showed a gradual increase that was proportional to the SD deprivation time, followed by a decrease after 1 night of sleep restoration. These findings demonstrate a hyperalgesic modification to pain perception (as reflected by the augmented VAS) and a concomitant increase in the LEP threshold following T-SD, an apparently contradictory effect that can be explained by differences in the ways that attention affects these pain measurements.     

睡眠剥夺对大鼠动脉粥样硬化的影响

目的探讨睡眠剥夺（sleep deprivation,SD）对动脉粥样硬化（atherosclerosis,AS）进程的影响及其机制。方法 50只Wistar AS雄性大鼠随机分为5组（每组10只）：AS组、SD1d组、SD3d组、SD5d组、SD7d组。建立AS大鼠SD模型,制备主动脉组织标本,苏木精伊红（hematoxylin and eosin,HE）染色,光镜观察切片。检测主动脉组织还原型谷胱甘肽（glutathione,GSH）及脂质过氧化物丙二醛（malondialdehyde,MDA）含量、谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）及超氧化物歧化酶（superoxide dismutase,SOD）活性。检测血清肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）、高敏C反应蛋白（hypersensitivity-C reactive protein,hsCRP）、白细胞介素6（interleukin-6,IL-6）水平。结果随着睡眠剥夺时间的延长,大鼠AS病变进展逐渐加重。主动脉组织GSH含量逐渐降低,MDA含量逐渐增高,GSH-Px及SOD活性逐渐降低。血清中TNF-α、hsCRPI、L-6水平也在逐渐增高。结论睡眠剥夺可通过引起机体的氧化应激反应及加速炎症发展,从而促进AS进程。     

睡眠剥夺对大鼠学习能力和海马乙酰胆碱含量的影响

目的研究不同持续时间睡眠剥夺(SD)对大鼠学习能力以及海马乙酰胆碱(Ach)含量的影响。方法采用小平台水环境法建立睡眠剥夺模型,以正常组作为对照,使用Y型迷宫测试不同持续时间睡眠剥夺对大鼠学习能力的影响,采用碱性羟胺比色法测定海马乙酰胆碱含量变化。结果与正常对照组相比,睡眠剥夺4 d、6 d组学习成绩明显降低,海马乙酰胆碱含量明显减少,睡眠剥夺2 d组学习成绩明显提高,海马乙酰胆碱含量无显著差异。结论睡眠剥夺导致的大鼠学习能力下降可能与其海马乙酰胆碱含量减少有关。     

BDNF in sleep,insomnia, and sleep deprivation

The protein brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors involved in plasticity of neurons in several brain regions. There are numerous evidence that BDNF expression is decreased by experiencing psychological stress and that, accordingly, a lack of neurotrophic support causes major depression. Furthermore, disruption in sleep homeostatic processes results in higher stress vulnerability and is often associated with stress-related mental disorders. Recently, we reported, for the first time, a relationship between BDNF and insomnia and sleep deprivation (SD). Using a biphasic stress model as explanation approach, we discuss here the hypothesis that chronic stress might induce a deregulation of the hypothalamic-pituitary-adrenal system. In the long-term it leads to sleep disturbance and depression as well as decreased BDNF levels, whereas acute stress like SD can be used as therapeutic intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial SD (PSD) induced a fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase.

• Key messages

• Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of stress-related mood disorders.

• The interplay of stress and sleep impacts on BDNF level.

• Partial sleep deprivation (PSD) shows a fast action on BDNF level increase.

     

Effects of female sex hormones on responses to CGRP, acetylcholine, and 5-HT in rat isolated arteries

BACKGROUND: Female sex hormones are implicated in the modulation of reactivity of a wide range of blood vessels under physiological as well as pathological conditions. Migraine, a neurovascular syndrome, is 3 times more prevalent in women during their reproductive period than in men. OBJECTIVE: This study sets out to investigate the effects of the female sex steroids, 17beta-estradiol and progesterone (separately and in combination) on vasoactive responses to calcitonin gene-related peptide (CGRP), acetylcholine, and 5-hydroxytryptamine (5-HT) in rat isolated mesenteric, caudal, and basilar arteries. METHODS: Female Sprague-Dawley rats were ovariectomized (Day 0) and 7 days later subcutaneously implanted with pellets releasing over a 21-day period 17beta-estradiol (0.25 mg), progesterone (50 mg), their combination, or placebo. On days 25-28, the animals were killed, arteries isolated and mounted in Mulvany myographs, and cumulative concentration response curves to CGRP, acetylcholine, and 5-HT were constructed. RESULTS: The relaxant responses to CGRP were significantly potentiated in mesenteric and caudal arteries from rats treated with 17beta-estradiol as compared to the placebo-treated rats. Acetylcholine-induced relaxations were potentiated in the caudal artery from rats treated with the combination of 17beta-estradiol and progesterone, as compared to that from placebo-treated rats. The 5-HT-induced contractions in the 3 arteries were not significantly different in efficacy or potency. CONCLUSION: Our results show that 17beta-estradiol potentiates CGRP-induced relaxations in the mesenteric and caudal arteries, while the combination treatment enhances acetylcholine-induced relaxations in the caudal artery. Although these in vitro experiments have been carried out in rats and a direct extrapolation to migraine in humans is not possible, our results may provide a new avenue to study the effects of sex steroids on vascular reactivity.