胰岛素在大鼠深慢波睡眠调节中的作用

目的 探讨胰岛素对大鼠睡眠特别是深慢波睡眠的影响. 方法根据SD大鼠海马CA1区注射试剂及剂量的不同,分为对照组、0.05 IU胰岛素组、0.1 IU胰岛素组和0.2 IU胰岛素组;采用脑立体定位、核团插管、微量注射和多导睡眠描记技术观察海马CA1区微量注射胰岛素对大鼠睡眠-觉醒周期的影响. 结果海马CA1区微量注射0.05 IU的胰岛素对大鼠睡眠-觉醒周期及睡眠的深度无明显影响.微量注射0.1 IU的胰岛素后,觉醒时间减少,总睡眠时间增多;与对照组比较,慢波睡眠时间增加18.1%(P<0.05),且主要是浅慢波睡眠成分增加22.0%(P<0.01).微量注射0.2 IU的胰岛素后,觉醒时间减少,总睡眠时间增多,睡眠加深;与对照组比较,慢波睡眠时间增加29.8%(P<0.01),其中浅慢波睡眠时间增加21.6%(P<0.01),深慢波睡眠时间增加53.2%(P<0.05).结论 胰岛素在海马参与睡眠的调节且具有促眠作用,胰岛素对大鼠睡眠深度的影响与注射的剂量呈正相关.     

大鼠腹外侧视前区P物质对睡眠的影响及其作用机制的研究

目的探讨大鼠下丘脑腹外侧视前区(vLPO)中P物质(SP)对睡眠的影响及其作用机制。方法SD大鼠120只,分实验组(64只)和对照组(16只),40只不符合要求剔除。采用脑立体定位、核团插管、微量注射、多导睡眠描记和免疫组织化学染色等方法观察vLPO中SP对睡眠的影响及其机制。结果大鼠下丘脑vLPO内微量注射SP后与对照组比较睡眠时间增加13.1%,特别是深慢波睡眠,觉醒时间减少22.0%;而在vLPO内微量注射SP受体阻断剂后睡眠时间减少19.6%,觉醒时间增加31.9%。vLPO内微量注射磷脂酶C抑制剂U73122或γ-氨基丁酸(GABA)合成关键酶(谷氨酸脱羧酶)抑制剂3-巯基丙酸均可阻断SP的促眠作用。结论SP在大鼠vLPO中具有促进睡眠,特别是提高深慢波睡眠的作用,该效应可能是通过vLPO中GABA能神经元介导的。     

淫羊藿总黄酮对大鼠睡眠-觉醒影响的观察

目的 观察侧脑室注射淫羊藿总黄酮(total flavonoids of Epimedium,TFE)对大鼠睡眠和觉醒活动的影响.方法 运用脑立体定位技术进行TFE的侧脑室微量注射,通过多导睡眠描记术(PSG)观察TFE对大鼠睡眠-觉醒活动的影响.结果 侧脑室注射TFE引起大鼠慢波睡眠时间(SWS)和总睡眠时间(TST)增多,觉醒(W)时间减少;侧脑室注射荷包牡丹碱(Bic)可增加W,减少快波睡眠(PS);侧脑室同时注射TFE和Bic则对睡眠和W无显著效应.结论 TFE可促进睡眠,抑制觉醒,即TFE具有明显的中枢抑制作用.     

天麻乙酸乙酯提取物对血管性痴呆大鼠海马CA1区锥体细胞的影响

目的观察天麻乙酸乙酯提取物对血管性痴呆模型大鼠海马CA1区锥体细胞的影响。方法采用双侧颈总动脉永久性结扎法,造成慢性脑灌注不足所致SD大鼠血管性痴呆模型。造模6周后,40只大鼠随机分为5组,假手术组、模型组、尼莫地平组、天麻乙酸乙酯提取物高剂量组(高剂量组)和天麻乙酸乙酯提取物低剂量组(低剂量组),每组8只。给药3周后,HE染色检测海马锥体细胞的变化。结果与假手术组比较,模型组大鼠海马CA1区锥体细胞数目明显减少(P<0.01);与模型组比较,尼莫地平组和高剂量组大鼠海马CA1区锥体细胞数目明显增多(P<0.01),低剂量组大鼠海马CA1区锥体细胞数目无明显变化(P>0.05)。结论天麻乙酸乙酯提取物能改善血管性痴呆大鼠脑组织海马CA1区锥体细胞的病理改变。     

新型IL-10抑制剂对睡眠剥夺大鼠的影响

目的 研究不同剂量AS101对于6 h睡眠剥夺后大鼠睡眠觉醒周期的影响.方法 采用脑立体定位、脑电图、肌电图记录方法 观察AS101对于睡眠剥夺大鼠睡眠反跳的影响.结果 6 h睡眠剥夺后,与注射缓冲液组(PBS)大鼠比较,0.5 mg/kg AS101可以增加觉醒时间和减少慢波睡眠时间,可将快眼动睡眠从(54.53±14.61)min减少到(34.4±17.34)min(P＜0.05).结论 AS101可能参与大鼠睡眠觉醒周期的调节.     

重组腺相关病毒神经肽Y基因转染对海人酸致痫大鼠癫痫发作及海马苔藓纤维出芽的影响

目的探讨重组腺相关病毒神经肽Y(rAAV2/1-NPY-EGFP)基因转染对癫痫发作和海马苔藓纤维出芽的影响。方法清洁级健康Wistar大鼠30只,体重250～270 g,随机分成NPY实验组(n=12),阳性对照组(n=12)和空白对照组(n=6)。实验组:脑室注射10μl的rAAV2/1-NPY-EGFP,滴度为5×1011μg/ml;阳性对照组在脑室内注射等量的生理盐水。以上两组10 min后分别在海马CA3区注射海人酸(KA);空白对照组依次分别在脑室和CA3区注射等量的生理盐水。并分别于注射后2、4 w观察大鼠的癫痫发作情况,视频脑电(EEG)癫痫波的频率和波幅,Timm染色观察海马CA3区苔藓纤维出芽。结果 NPY实验组大鼠随观察时间的延长,发作程度逐渐减轻,与阳性对照组大鼠相比,于4 w时,脑电图癫痫波放电频率减少(P<0.05),波幅降低(P<0.05)。NPY实验组苔藓纤维出芽分级明显低于对照组。空白对照组没有癫痫发作,CA3区苔藓纤维出芽没有明显变化。结论 rAAV2/1-NPY-EGFP基因转染可以降低海马CA3区苔藓纤维出芽程度,有效抑制癫痫发作,为NPY基因治疗临床难治性癫痫提供了有力试验支持。     

丁苯酞对血管性痴呆大鼠海马CA1区Bax和Bcl-2表达的影响

目的观察丁苯酞(NBP)对血管性痴呆(VD)大鼠海马CA1区凋亡调控基因Bax和Bcl-2表达的影响,探讨NBP对VD的保护作用。方法将80只健康Wistar大鼠随机分为VD组(VD模型)、NBP治疗组(VD模型+NBP)、NBP对照组(假手术+NBP)、Sham组(假手术组),每组20只,每组又分为4个亚组:术后1、2、4、8 w,每个亚组5只。永久性双侧颈总动脉结扎法制备VD大鼠模型。NBP对照组和NBP治疗组大鼠术后1 d开始给予BNP腹腔注射,剂量为5 mg·kg~(-1)·d~(-1),Sham组和VD组给予生理盐水腹腔注射(0.2 ml/d)。各组大鼠连续腹腔注射给药7 d。术后各时间点(1、2、4、8 w)留取海马组织,免疫组化观察各组大鼠海马CA1区Bax和Bcl-2的表达。结果VD组大鼠海马CA1区Bax蛋白表达灰度明显高于Sham组(P<0.05);4 w和8 w时,NBP治疗组大鼠海马CA1区Bax蛋白表达均明显低于VD组大鼠相应时间点(P<0.05)。8 w时VD大鼠海马CA1区Bax表达灰度明显高于1 w和2 w时(P<0.05)。NBP对照组大鼠海马CA1区Bcl-2表达灰度均明显高于Sham组(P<0.05);8 w时NBP治疗组大鼠海马CA1区Bcl-2表达灰度明显高于VD组(P<0.05)。结论VD大鼠海马CA1区促凋亡蛋白Bax过度表达,抗凋亡蛋白Bcl-2的表达有减弱趋势;NBP对VD大鼠海马CA1区细胞凋亡具有明显的保护作用,可以抑制缺血损伤导致的海马CA1区Bax蛋白过度表达,同时能够提高大鼠海马CA1区Bcl-2蛋白的表达水平,抑制细胞凋亡,促进细胞存活,发挥神经保护作用。     

淀粉样蛋白联合L-型谷氨酸诱导类阿尔茨海默病模型

目的采用淀粉样蛋白联合L-型谷氨酸诱导建立类阿尔茨海默病(AD)大鼠模型。方法将β-淀粉样蛋白25～35(Aβ25～35)注射到大鼠双侧CA3区,或联合L-谷氨酸(Glu)分别注射到大鼠双侧CA3区、侧脑室制备类AD模型,用Morris水迷宫和免疫组化方法分别检测大鼠学习记忆力和胆碱乙酰转移酶(ChAT)及NMDAR1脑内表达。结果 Aβ联合Glu诱导的类AD模型大鼠学习记忆力明显降低,与假手术组和单纯Aβ注射组相比,均有统计学差异(P<0.01或P<0.05),同时海马CA3区及顶叶皮质内ChAT及NMDR1表达也降低明显(P<0.01)。结论采用淀粉样蛋白联合L-型谷氨酸诱导建立类AD动物模型比单纯Aβ注射效果好,能模拟出AD学习记忆力减退和相关的主要病理学变化。     

IGF-1对Alzheimer大鼠认知功能和海马Aβ1-40表达的影响

目的建立凝聚态淀粉样蛋白(Aβ1-40)诱导的模拟老年性痴呆(Alzheimer’s disease,AD)动物模型,观察Aβ1-40对Wister大鼠行为学及病理的改变,以及皮下注射胰岛素样生长因子-1(IGF-1)对拟AD模型大鼠学习记忆能力和海马CA1区淀粉样蛋白(Aβ1-40)表达的影响。方法设立正常组、拟AD模型组、盐水治疗对照组及IGF-1治疗组共4组。采用凝聚态Aβ1-40进行海马CA1区微量注射建立拟AD大鼠模型,术后第二天治疗组分别皮下注射生理盐水(1ml/kg)和IGF-1(50μg/kg)。造模2周后4组分别进行水迷宫行为学试验检测大鼠学习记忆能力,用药3周后行病理学检查(包括HE、刚果红)和免疫组化方法观察海马CA1区Aβ1-40的表达。结果 IGF-1组与拟AD模型组比较,定位航行试验第3天开始平均逃避潜伏期明显缩短(P<0.05),在空间探索试验中,跨越原平台位置的次数明显增多(P<0.01)。拟AD模型组和盐水治疗组海马点附近可见颗粒细胞带明显受损,弥漫性胶质细胞浸润,局部神经元大量缺失,细胞排列疏松紊乱,IGF-1组海马注射区可见颗粒细胞带轻度受损,神经元排列尚规则,与模型组之间有统计学意义(P<0.01)。IGF-1组大鼠海马CA1区Aβ1-40的表达,与拟AD模型组比较明显减少(P<0.01),生理盐水对治疗没有影响。结论凝聚态Aβ1-40海马注射可以模拟AD的学习记忆障碍和神经元损伤等行为学和病理学特征。IGF-1减少海马CA1区Aβ1-40的表达,减轻凝聚态Aβ1-40对大鼠海马的病理损害,有显著改善拟AD模型大鼠学习记忆能力和病理改变的作用。     

脑舒胶囊对Aβ_(25～35)诱导的AD大鼠海马神经元氧化应激的保护作用

目的研究脑舒胶囊对Aβ25～35诱导的阿尔茨海默病(AD)大鼠海马神经元氧化应激的保护作用。方法双侧脑室注射Aβ25～35复制大鼠AD模型;Morris水迷宫观察大鼠学习记忆能力;化学比色法检测海马组织谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;HE染色,光镜观察海马CA3区神经元损伤情况。结果与对照组比较,AD模型大鼠学习记忆能力明显下降(P0.05),海马组织GSH-Px、SOD活性明显下降(P0.05,P0.01),MDA含量明显增加(P0.05,P0.01);与模型组比较,脑舒胶囊治疗组大鼠学习记忆力明显改善,海马组织GSH-Px、SOD活性明显升高(P0.05,P0.01),MDA含量明显下降(P0.05,P0.01);光镜观察发现,模型组大鼠海马CA3区神经元排列紊乱,细胞数量减少;细胞体积变小,胞体形状不规则,胞浆浓缩,胞核固缩深染,结构不清,脑舒胶囊治疗组大鼠海马CA3区神经元上述情况明显改善。结论脑舒胶囊对Aβ25～35所致AD大鼠海马神经元氧化应激具有较好的保护作用。     

Circadian variation of plasma catecholamines in young and old men: relation to rapid eye movement and slow wave sleep.

Young and old healthy subjects with indwelling venous cannulae were found to undergo significant diurnal variations in plasma catecholamine levels. Both norepinephrine and epinephrine levels peaked in late morning and reached lowest values at night during sleep. Catecholamine levels were similar during slow wave and rapid eye movement sleep. While epinephrine levels were unaffected by age, norepinephrine levels were greater in older subjects by 28% during the day (at 1100 h; P less than 0.01) and by 75% at night (between 2200--0900 h; P less than 0.01). Older subjects slept less well; they had 90% less stage 4 sleep, 27% less rapid eye movement sleep, and twice as much wakefulness at night (P less than 0.05). These findings raise the possibility that this well known age effect on sleep may be related to increased sympathetic nervous system activity.     

Sleep deprivation effects on the activity of the hypothalamic–pituitary–adrenal and growth axes: potential clinical implications

OBJECTIVES: Although several studies have shown that sleep deprivation is associated with increased slow wave sleep during the recovery night, the effects of sleep deprivation on cortisol and growth hormone (GH) secretion the next day and recovery night have not been assessed systematically. We hypothesized that increased slow wave sleep postsleep deprivation is associated with decreased cortisol levels and that the enhanced GH secretion is driven by the decreased activity of the HPA axis. DESIGN AND SUBJECTS: After four consecutive nights in the Sleep Laboratory, 10 healthy young men were totally deprived of sleep during the fifth night, and then allowed to sleep again on nights six and seven. Twenty-four hour blood sampling was performed serially every 30 minutes on the fourth day, immediately following the previous night of sleep and on the sixth day, immediately after sleep deprivation. MEASUREMENT: Eight-hour sleep laboratory recording, including electroencephologram, electro-oculogram and electromyogram. Plasma cortisol and GH levels using specific immunoassay techniques. RESULTS: Mean plasma and time-integrated (AUC) cortisol levels were lower during the postdeprivation nighttime period than on the fourth night (P < 0.05). Pulsatile analysis showed significant reduction of both the 24 h and daytime peak area (P < 0.05) and of the pulse amplitude (P < 0.01), but not of the pulse frequency. Also, the amount of time-integrated GH was significantly higher for the first 4 h of the postdeprivation night compared to the predeprivation night (P < 0.05). Cross-correlation analyses between the absolute values of the time-series of each hormone value and percentage of each sleep stage per half hour revealed that slow wave sleep was negatively correlated with cortisol and positively correlated with GH with slow wave sleep preceding the secretion of these hormones. In contrast, indices of sleep disturbance, i.e. wake and stage 1 sleep, were positively correlated with cortisol and negatively correlated with GH. CONCLUSION: We conclude that sleep deprivation results in a significant reduction of cortisol secretion the next day and this reduction appears to be, to a large extent, driven by the increase of slow wave sleep during the recovery night. We propose that reduction of CRH and cortisol secretion may be the mechanism through which sleep deprivation relieves depression temporarily. Furthermore, deep sleep has an inhibitory effect on the HPA axis while it enhances the activity of the GH axis. In contrast, sleep disturbance has a stimulatory effect on the HPA axis and a suppressive effect on the GH axis. These results are consistent with the observed hypocortisolism in idiopathic hypersomnia and HPA axis relative activation in chronic insomnia. Finally, our findings support previous hypotheses about the restitution and immunoenhancement role of slow wave (deep) sleep.     

Alpha sleep characteristics in fibromyalgia

OBJECTIVE: To characterize the patterns of alpha electroencephalographic sleep and their associations with pain and sleep in patients with fibromyalgia. METHODS: Pain and sleep symptoms of 40 female patients with fibromyalgia and 43 healthy control subjects were studied before and after overnight polysomnography. Blinded analyses of alpha activity in non-rapid eye movement (non-REM) sleep were performed using time domain, frequency domain, and visual analysis techniques. RESULTS: Three distinct patterns of alpha sleep activity were detected in fibromyalgia: phasic alpha (simultaneous with delta activity) in 50% of patients, tonic alpha (continuous throughout non-REM sleep) in 20% of patients, and low alpha activity in the remaining 30% of patients. Low alpha activity was exhibited by 83.7% of control subjects (P < 0.01). All fibromyalgia patients who displayed phasic alpha sleep, activity reported worsening of pain after sleep, compared with 58.3% of patients with low alpha activity (P < 0.01) and 25.0% of patients with tonic alpha activity (P < 0.01). Postsleep increase in the number of tender points occurred in 90.0% of patients with phasic alpha activity, 41.7% of patients with low alpha activity, and 25.0% of patients with tonic alpha activity (P < 0.01). Self ratings of poor sleep were reported by all patients with phasic alpha activity, 58.3% of patients with low alpha activity (P < 0.01), and 12.5% of patients with tonic alpha activity (P < 0.01). Patients with phasic alpha activity reported longer duration of pain than patients in other subgroups (P < 0.01). Additionally, patients with phasic alpha sleep activity exhibited less total sleep time than patients in other subgroups (P < 0.05), as well as lower sleep efficiency (P < 0.05) and less slow wave sleep (P < 0.05) than patients with a tonic alpha sleep pattern. CONCLUSION: Alpha intrusion during sleep can be of different patterns. Phasic alpha sleep activity was the pattern that correlated better with clinical manifestations of fibromyalgia.     

Effects of captopril and oxygen on sleep apnoea in patients with mild to moderate congestive cardiac failure.

OBJECTIVES--To determine the effects of captopril and oxygen on sleep quality in patients with mild to moderate cardiac failure. DESIGN--An open observational study. PATIENTS--12 patients with New York Heart Association class II-III heart failure were studied at baseline. 9 of these patients were then examined at the end of 1 month of treatment with captopril; 9 of the patients were separately assessed during a single night of supplementary oxygen. MAIN OUTCOME MEASURES--Sleep patterns by polysomnography, overnight oximetry, and subjective sleep assessment using visual analogue scores. RESULTS--Abnormal sleep was present in all baseline studies. Complete polysomnograms after treatment with captopril were obtained in 8 patients. Light sleep (stages 1 and 2) was reduced (mean (SEM) 61%(8)% to 48%(6)% actual sleep time, P < 0.05) but slow wave (stages 3 and 4) and REM (rapid eye movement) sleep increased (25%(6)% to 31%(5)%, 14%(2)% to 21%(5)% actual sleep time, P < 0.05). Apnoeic episodes (242(59) to 118(30), P < 0.05), desaturation events (171(60) to 73(37), P < 0.05), and arousals (33(5) to 18(3) P < 0.01) were reduced. Visual analogue scores of sleep quality increased 49(5) to 69(5), P < 0.01). Complete polysomnograms were obtained in 7 patients treated with oxygen. Light sleep duration was reduced (55% (7)% to 42%(5)% actual sleep time, P < 0.05) and slow wave sleep increased (30%(5)% to 38%(6)% actual sleep time, P < 0.05). REM sleep duration was not significantly different. Total arousals (33(6)% to 20(2) P < 0.05), desaturation events (140(33) to 38(10), P < 0.01), and apnoeic episodes (212(53) to 157(33), P < 0.05) were reduced. Visual analogue scores of sleep quality were unchanged. CONCLUSIONS--Captopril and oxygen may improve sleep quality and reduce nocturnal desaturation in patients with mild to moderate cardiac failure. Improved sleep quality could explain the reduction in daytime symptoms seen after treatment in patients with chronic heart failure.     

Effects of morphine and naloxone on plasma levels of LH, FSH, prolactin and growth hormone in the immature male pig

The effects of acute i.v. administration of gonadotrophin-releasing hormone (GnRH; 0.1 micrograms/kg), morphine (3 mg/kg) and/or naloxone (0.5 mg/kg) on LH and FSH secretion was evaluated in young male pigs (approximately 6 weeks old) with venous brachiocephalic cannulae. The effects of morphine and/or naloxone treatments on prolactin and GH were also evaluated. The influence of morphine on hypophysial hormone secretion was also examined 2 days after castration. Animals treated with morphine and/or naloxone were compared with saline-injected control animals. Injection of GnRH induced 400 and 50% increases in LH and FSH respectively. Morphine and/or naloxone did not influence LH secretion in intact or castrated animals. Morphine suppressed (P less than 0.01) FSH levels 40-60 min after injection whereas naloxone had no effect. Castration eliminated morphine-induced suppression of FSH. Injection of morphine followed by naloxone resulted in acutely raised (P less than 0.05) FSH concentrations. Morphine induced a threefold increase (P less than 0.01) in prolactin within 30 min of injection and naloxone inhibited the effect of morphine. Levels of GH were increased (P less than 0.01) 20 min after morphine treatment and this increase was delayed when naloxone was given immediately after morphine. Naloxone alone did not affect prolactin or GH secretion. Castration caused increases in LH (P less than 0.05) and FSH (P less than 0.01), did not influence prolactin or GH, and reduced plasma testosterone to undetectable (less than 1.0 nmol/l) levels. These results suggest that in young male pigs the hypothalamic-hypophysial axis is responsive to GnRH and gonadal negative feedback.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained effect of continuous positive airway pressure on baroreflex sensitivity in congestive heart failure patients with obstructive sleep apnea

BACKGROUND: Patients with either heart failure or obstructive sleep apnea have a reduced baroreflex sensitivity for heart rate, a sign of poor prognosis. We previously demonstrated that nocturnal application of continuous positive airway pressure to heart failure patients with obstructive sleep apnea increased baroreflex sensitivity acutely, but it is not known whether these effects persist into wakefulness. OBJECTIVE: To determine whether treating obstructive sleep apnea in heart failure patients with continuous positive airway pressure improves baroreflex sensitivity during wakefulness. METHODS: Spontaneous baroreflex sensitivity was assessed during wakefulness in 33 heart failure patients (left ventricular ejection fraction < or = 45%) with obstructive sleep apnea (apnea-hypopnea index > or = 20). Subsequently, baroreflex sensitivity was reassessed 1 month after patients were randomly allocated to nocturnal continuous positive airway pressure treatment or no treatment (control). RESULTS: Compared with the 14 control patients, the 19 continuous positive airway pressure-treated patients experienced a greater increase in baroreflex sensitivity [median, (25%, 75%)] [from 5.4 (2.2, 8.3) to 7.9 (4.4, 9.4) ms/mmHg; P = 0.01] and left ventricular ejection fraction (P < 0.001). In addition, daytime systolic blood pressure and heart rate decreased more in the continuous positive airway pressure group (from 122 +/- 15 to 113 +/- 12 mmHg; P = 0.02, and from 66 +/- 8 to 62 +/- 8 bpm; P < 0.001, respectively) than in the control group. CONCLUSION: Treatment of coexisting obstructive sleep apnea by continuous positive airway pressure in heart failure patients improves baroreflex sensitivity during wakefulness in addition to improving left ventricular ejection fraction and lowering blood pressure and heart rate. These data indicate that the improved autonomic regulation of heart rate in heart failure patients treated for obstructive sleep apnea during sleep persists into wakefulness.     

β内啡肽对慢性缺氧大鼠呼吸的影响

目的　探讨β内啡肽（βＥＰ） 在慢性缺氧大鼠呼吸调控中的作用。方法　采用放射免疫法测定慢性缺氧大鼠模型血浆及延髓、桥脑、下丘脑、中央灰质等神经核团中βＥＰ的含量变化，以及不同给药途径给予外源性βＥＰ对慢性缺氧大鼠呼吸功能的影响。正常大鼠侧脑室注射βＥＰ后，观察记录呼吸频率（ＲＲ） ；１０２ 只慢性缺氧大鼠随机分为：（１） 静脉组３６ 只，分别给予阿片受体拮抗剂纳洛酮（ＮＬＸ） 和不同剂量βＥＰ，记录ＲＲ 和潮气量（ＶＴ）；（２） 侧脑室组４８ 只，微量注射ＮＬＸ、βＥＰ，测定ＲＲ、ＶＴ及血气指标；（３） 孤束核组１８ 只，分别注射βＥＰ和人工脑脊液（ＡＣＳＦ） ，测定ＲＲ和ＶＴ。结果慢性缺氧模型延髓、桥脑、下丘脑、中央灰质和血浆βＥＰ的含量较对照组均显著升高（Ｐ＜０－０１）。给正常大鼠侧脑室注射βＥＰ后，ＲＲ 显著下降（ Ｐ＜ ０－０５） 。慢性缺氧大鼠静脉给予不同剂量βＥＰ和ＮＬＸ后，ＲＲ和ＶＴ 变化差异无显著性（Ｐ＞０－０５）。侧脑室注射ＮＬＸ后，ＲＲ显著增高（ Ｐ＜０－０５）。侧脑室及孤束核注射βＥＰ后显著降低ＲＲ、ＶＴ。侧脑室注射ＮＬＸ３０ 分钟时ＭＶ／ＰａＣＯ２ 较对照组显著升高（ｔ＝２－７６ ，     

Middle-aged men show higher sensitivity of sleep to the arousing effects of corticotropin-releasing hormone than young men: clinical implications

The prevalence of insomnia associated with emotional stress increases markedly in middle-age. Both the top and end hormones of the hypothalamic-pituitary-adrenal axis, i.e. CRH and glucocorticoids, stimulate arousal/wakefulness and inhibit slow wave (deep) sleep in experimental animals and man. The objective of this study was to test the hypothesis that middle-age is characterized by increased sensitivity to the sleep-disturbing effects of the hypothalamic-pituitary-adrenal axis. We studied 12 healthy middle-aged (45.1 +/- 4.9) and 12 healthy young (22.7 +/- 2.8) men by monitoring their sleep by polysomnography for 4 consecutive nights, including in tandem 1 adaptation and 2 baseline nights and a night during which we administered equipotent doses of ovine CRH (1 microg/kg, iv bolus) 10 min after sleep onset. Analyses included comparisons within and between groups using multiple ANOVA and regression analysis. Although both middle-aged and young men responded to CRH with similar elevations of ACTH and cortisol, the former had significantly more wakefulness and suppression of slow wave sleep compared with baseline sleep; in contrast, the latter showed no change. Also, comparison of the change in sleep patterns from baseline to the CRH night in the young men to the respective change observed in middle-aged men showed that middle-age was associated with significantly higher wakefulness and significantly greater decrease in slow wave sleep than in young age. We conclude that middle-aged men show increased vulnerability of sleep to stress hormones, possibly resulting in impairments in the quality of sleep during periods of stress. We suggest that changes in sleep physiology associated with middle-age play a significant role in the marked increase of prevalence of insomnia in middle-age.     

Brief wake episodes modulate sleep-inhibited luteinizing hormone secretion in the early follicular phase

To determine the influence of sleep, sleep stage, and time of day on the dynamics of pulsatile LH secretion in the early follicular phase (EFP) of the menstrual cycle, 11 normal women underwent simultaneous polysomnographic monitoring of sleep and measurement of LH in frequent sampling studies during a 40-h protocol that consisted of one night of normal sleep and one night of sleep deprivation followed by an afternoon nap. The interpulse interval of LH was longer during sleep than wake whether it occurred at night or during the day (P < 0.002), implying a decrease in GnRH pulse frequency associated with sleep in the EFP. LH pulse amplitude was greater during sleep than wake (P < 0.001) and greater pulse amplitudes were associated with longer interpulse intervals during sleep (P < 0.005), but not wake. An interaction between sleep and time of day was observed for mean LH, with lower mean LH levels during sleep than wake at night (P < 0.02), but not during the day. Wakefulness was more likely to be associated with an LH pulse than were stages I/II, III/IV (slow wave), or rapid eye movement sleep (P < 0.005). In addition, the probability of wakefulness within the sleep episode increased 5-15 min before the onset of LH pulses (relative to randomly selected nonpulse LH; P < 0.05), suggesting that wakefulness was the primary event. In the absence of sleep, there was an effect of time of day on mean LH (P < 0.02) and LH pulse amplitude (P < 0.03), with greatest values seen during the evening. In conclusion, in the EFP, inhibition of LH pulse frequency is related to sleep rather than time of day. During periods of sleep, LH pulses occur most commonly in association with brief awakenings, suggesting that interruptions from sleep allow escape from the inhibitory effect of sleep on pulsatile GnRH secretion. A separate effect of time of day on LH pulse dynamics in the absence of sleep was also observed with evening augmentation of LH pulse amplitude and mean level; however, additional studies will be required to determine whether this represents a true circadian effect.