中枢性乙酰胆碱释放与睡眠、温度和皮肤感觉刺激的关系

广泛分布于中枢神经系统的乙酰胆碱所介导的胆碱能传递系统在自然睡眠的发生和全麻作用机制上都起着至关重要的作用。中枢性乙酰胆碱与全麻药的作用机制、自然睡眠及体温、皮肤感觉刺激的关系。     

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。     

帕金森病患者神经递质网络与乙酰胆碱代谢的关系

帕金森病(PD)是一种发生于中老年期的,缓慢进展的神经系统退行性疾病。我国>65岁人群患病率约占1.70%[1],>80岁人群的患病率约为2.65%[2]。PD的典型特征是中脑黑质多巴胺能神经元变性坏死,当多巴胺减少达70%以上时,则出现静止性震颤、肌肉僵直等一系列症状,但仅多巴胺的缺失不能完全解释其临床异质性。有研究者发现某些非多巴胺能神经递质参与PD的发病,可能引起患者发生诸如痴呆、抑郁症、行为和睡眠障碍、自主神经调节障碍等临床问题[3]。脑内许多神经元能释放多种神经递质,这些神经递质可能有类似的突触后效应,也可能有不同或增强效应[4]。有研究者发现,中脑被盖区及黑质多巴胺神经末梢的激动能激发伏隔核谷氨酸介导的兴奋性电冲动[5]。在海马、纹状体等部位存在自主胆碱能神经元,包含1%~2%的胆碱能中间神经元[6]。     

海拔高度对人体睡眠结构和神经机能的影响

很多研究表明高原人体各系统功能存在有不同程度的生理变化。高原入神经机能及睡眠结构的改变早已为人们所关注。但是,海拔高度对人体神经机能和夜间睡眠结构具体有什么样的影响还缺乏深入研究。我们认为开展高原睡眠生理研究可进一步探索高原生理及某些疾病发生、发展的规律,更好地为世居、移居高原的各族人民健康服务。因此,我们在青海省果洛州(海拔3730米)对当地的8例健康成人及抵平原(苏州、海拔10米)的12例青海省天峻县(海拔3500～3700米)健     

睡眠与心血管疾病的关系

本文阐述在睡眠阶段出现的独特的自主神经活动、血流动力学和呼吸系统的改变与心血管疾病，尤其是心脏突发事件的密切关系。     

中枢性睡眠呼吸暂停综合征与慢性充血性心力衰竭

目的：分析中枢性睡眠呼吸暂停综合征(central sleep apnea syndrome，CSAS)与慢性充血性心力衰竭的关系。方法：根据近年来国内外的相关研究总结慢性心力衰竭患CSAS的发病率情况，介绍了其与心力衰竭的相互影响，综述了目前在发病机制研究方面的取得的进展以及治疗手段的改善等。重点讨论了慢性充血性心力衰竭患发生CSAS的病理机制。总结了现有治疗方法的实际疗效，并详细介绍了最新用于治疗中枢性睡眠呼吸暂停的自动伺服通气设备(AutoSet CS)的工作原理。结果：慢性心力衰竭伴CSAS的患预后明显比不伴CSAS的患差，循环时间的延迟、CO2化学感受器的敏感性的提高及其他大脑中枢和外周感受器对呼吸中枢的影响可能在其发病机制中有着重要的作用。AutoSet CS是目前治疗CSAS最为有效的可接受的无创通气技术。结论：必须进行长期的以存活率和健康状况为终点的前瞻性的随机对照研究，以评估对慢性心力衰竭患睡眠呼吸紊乱的纠正是否真的可以改善其预后。对慢性心力衰竭患睡眠呼吸紊乱现象的进一步研究将是今后睡眠医学研究的一个重要方向。     

神经肌肉接头中乙酰胆碱酯酶的研究进展

哺乳动物的神经肌肉接头（NMJ）作为运动神经末端和肌肉相连接的部位，是目前研究最多、了解最清楚的突触结构。NMJ乃至整个神经系统突触的发育过程就是突触前后膜特化性改变的过程：轴突末梢释放神经递质被突触后细胞接收，经过电一化学一电的转换，完成有效和准确的信息传递。早在20世纪30年代人们就开始了对NMJ的研究，到了20世纪70年代，大量有关NMJ发育的实验使人们认识到，运动系统突触的形成与神经和肌肉之间精确的信号传导有关。许多研究报道，乙酰胆碱酯酶（ACHE）可能作为一种特异性神经分泌蛋白，在胞内或胞外对神经元的增殖、突起的生长、NMJ的发育及AChR的丛聚有重要的作用，有关NMJ中AChE的研究不但对探讨中枢神经系统突触功能和作用提供了重要线索。也为临床研究运动系统损伤和修复奠定了理论依据。有关对NMJ中AChE的研究主要集中在20世纪70～80年代，在此之后关于NMJ和AChE的研究较少且进展缓慢。     

中枢性睡眠呼吸暂停综合征与慢性充血性心力衰竭

目的:分析中枢性睡眠呼吸暂停综合征(centralsleepapneasyndrome,CSAS)与慢性充血性心力衰竭的关系。方法:根据近年来国内外的相关研究总结慢性心力衰竭患者CSAS的发病率情况,介绍了其与心力衰竭的相互影响,综述了目前在发病机制研究方面的取得的进展以及治疗手段的改善等。重点讨论了慢性充血性心力衰竭患者发生CSAS的病理机制。总结了现有治疗方法的实际疗效,并详细介绍了最新用于治疗中枢性睡眠呼吸暂停的自动伺服通气设备(AutoSetCS)的工作原理。结果:慢性心力衰竭伴CSAS的患者预后明显比不伴CSAS的患者差,循环时间的延迟、CO2化学感受器的敏感性的提高及其他大脑中枢和外周感受器对呼吸中枢的影响可能在其发病机制中有着重要的作用。AutoSetCS是目前治疗CSAS最为有效的可接受的无创通气技术。结论:必须进行长期的以存活率和健康状况为终点的前瞻性的随机对照研究,以评估对慢性心力衰竭患者睡眠呼吸紊乱的纠正是否真的可以改善其预后。对慢性心力衰竭患者睡眠呼吸紊乱现象的进一步研究将是今后睡眠医学研究的一个重要方向。     

睡眠与心血管疾病的关系

本文阐述在睡眠阶段出现的独特的自主神经活动、血流动力学和呼吸系统的改变与心血管疾病，尤其是心脏突发事件的密切关系。     

分析儿童肥胖与睡眠习惯的关系

目的：分析儿童肥胖与睡眠习惯的关系。方法：选取2022年1月至2022年9月厦门市儿童医院收治的肥胖儿童60例作为观察组,选取同时期正常体质量儿童60例作为对照组,分析纳入研究儿童的睡眠习惯,并以睡眠习惯分析量表完善对于儿童睡眠习惯的评估,以明确儿童肥胖与睡眠习惯之间的关系,进而指导临床针对性地干预。结果：观察组儿童中睡眠习惯、睡眠行为、夜醒问题、晨起习惯、白天嗜睡分项及总评分均显著高于对照组,2组比较差异有统计学意义(P<0.05)。结论：肥胖儿童存在较为严重的睡眠障碍,提示肥胖与睡眠习惯存在着显著关联,在临床研究中,对于肥胖患儿家属,进行睡眠指导,纠正肥胖儿童的不良睡眠习惯,能够有效改善其肥胖严重程度,为临床干预提供参考意见。     

Relationships between choline uptake, acetylcholine synthesis and acetylcholine release in isolated rat atria

Isolated rat atria take up [3H]choline and synthesize [3H]acetylcholine (ACh). The uptake of [3H]choline has a high-affinity component with a Km of approximately 0.2 microM and a Vmax of approximately 6 fmol/min/mg wet wt. This high-affinity component of choline uptake is difficult to measure directly because it represents only a small portion of total [3H]choline uptake. However, the rate of synthesis of [3H] ACh from [3H]choline appears to reflect the activity of the high-affinity choline uptake system. Thus, [3H]ACh synthesis is most efficient at low choline concentrations and is inhibited in the presence of hemicholinium-3 and low NaCl medium. The neuronal localization of the [3H]Ach synthesized from [3H]choline is demonstrated by the finding that [3H]ACh is released from the atria by depolarization with 57 mM K+ medium. The release is Ca++ -dependent and there is a compensatory increase in the synthesis of [3H]ACh after depolarization-induced ACh release. These data suggest that [3H]choline can be specifically incorporated into a releasable pool of [3H]ACh localized in cardiac parasympathetic neurons. The synthesis of [3H]ACh is inhibited by blockade of high-affinity choline uptake and is regulated in response to neuronal activity. The application of these methods will provide a means for directly examining the physiological and pharmacological control of ACh synthesis and release from cardiac parasympathetic neurons.     

Psychophysical and cerebral responses to heat stimulation in patients with central pain, painless central sensory loss, and in healthy persons

Patients with central pain (CP) typically have chronic pain within an area of reduced pain and temperature sensation, suggesting an impairment of endogenous pain modulation mechanisms. We tested the hypothesis that some brain structures normally activated by cutaneous heat stimulation would be hyperresponsive among patients with CP but not among patients with a central nervous system lesion causing a loss of heat or nociceptive sensation with no pain (NP). We used H₂¹⁵O positron emission tomography to measure, in 15 healthy control participants, 10 NP patients, and 10 CP patients, increases in regional cerebral blood flow among volumes of interest (VOI) from the resting (no stimulus) condition during bilateral contact heat stimulation at heat detection, heat pain threshold, and heat pain tolerance levels. Both patient groups had a reduced perception of heat intensity and unpleasantness on the clinically affected side and a bilateral impairment of heat detection. Compared with the HC group, both NP and CP patients had more hyperactive and hypoactive VOI in the resting state and more hyperresponsive and hyporesponsive VOI during heat stimulation. Compared with NP patients, CP patients had more hyperresponsive VOI in the intralaminar thalamus and sensory-motor cortex during heat stimulation. Our results show that focal CNS lesions produce bilateral sensory deficits and widespread changes in the nociceptive excitability of the brain. The increased nociceptive excitability within the intralaminar thalamus and sensory-motor cortex of our sample of CP patients suggests an underlying pathophysiology for the pain in some central pain syndromes.     

Cutaneous sensory stimulation leading to facial flushing and release of calcitonin gene-related peptide

A patient is described with a 17-year history of intractable left-sided facial pain. The pain occurred daily in 5 sec spasms to a maximum of one every 2-3 min and was restricted to the left upper face. It was associated with rhinorrhoea on the left and often with ipsilateral facial flushing. Conventional therapy, including carbamazepine, baclofen and three posterior fossa explorations, had not provided lasting relief. Local facial stimulation by tapping a painful trigger point led to both pain and flushing of the face ipsilaterally. During this flushing, blood was collected and assayed using sensitive radioimmunoassays for several neuropeptides (neuropeptide Y, substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide). A marked (119%) increase in calcitonin gene-related peptide was noted in the external jugular vein blood ipsilaterally during the flushing with no change in the other peptides measured. To quantitate the effect of calcitonin gene-related peptide on human extracranial vessels, standard pharmacological procedures were used to examine the potency of the peptide as a vasodilator of human facial artery. The IC50 of calcitonin gene-related peptide for the prostaglandin F2 alpha-precontracted human facial artery was 10(-9) mol/l. The relevance of these observations to the clinical problem of migraine is considered.     

Presynaptic interactions between acetylcholine and adrenergic antagonists on norepinephrine release

A previously unknown interaction between acetylcholine (ACh) and adrenergic mechanisms is described, which increases the likelihood of a physiological association between the two divisions of the autonomic nervous system. In particular, ACh had a novel effect to disengage the neuronal mechanism that is purported to regulate the release of norepinephrine from sympathetic nerves. Brief exposure to ACh (1.4 X 10(-7) M-1.4 X 10(-5) M) inhibited the stimulation-evoked release of [3H]norepinephrine from guinea pig atria and ureter and rabbit aorta but higher concentrations (8.8 X 10(-5) or 1.4 X 10(-4) M) or prolonged exposure to moderate concentrations either had no visible effect or enhanced release. ACh blocked the ability of yohimbine, the presynaptic alpha receptor antagonist, to enhance the liberation of 3H-transmitter during field stimulation at 2 and 5 Hz, and it did so in all three of the test tissues. This effect was not attributable to a direct competition between ACh and yohimbine for presynaptic alpha sites and ACh did not act like yohimbine to increase transmitter release. The antagonistic effect of ACh bore no relation to the direct effect of ACh on adrenergic neurotransmitter release and occurred regardless of whether ACh itself inhibited, enhanced or did not affect transmitter liberation. Atropine blocked the effect of ACh on 3H-transmitter efflux and restored the capacity of yohimbine to enhance transmitter release. Inhibition of neurotransmitter release by norepinephrine was partially antagonized by ACh and this antagonism was also countered by atropine. Enhancement of norepinephrine release by phenoxybenzamine was also blunted by ACh. These findings cannot be incorporated into a model of neurotransmitter regulation that interprets the enhancement of norepinephrine release by adrenergic antagonists as the result of interruption of an on-going negative feedback system. The action of yohimbine appears linked to activation of presynaptic sites and not simply to their passive occupancy. A working model is offered to account for the interaction between ACh and adrenergic antagonists.     

不同时间点睡眠剥夺与星形胶质细胞的关系

目的探索大鼠不同时间点睡眠剥夺后脑干中缝核群星形胶质细胞 (astrocyte,AS)的反应. 方法采用小平台水环境法建立大鼠睡眠剥夺模型,用免疫组化的方法测量胶原纤维酸性蛋白( glial fibrillary acidic protein, GFAP)在脑干中缝核群的表达,分组为睡眠剥夺 3, 6, 12, 24, 96 h组,大平台对照组和正常单独饲养组,每组 4只. 结果睡眠剥夺后 GFAP在中缝核群均有表达,中缝苍白核和中缝背核有较高表达,随着睡眠剥夺时间的延长,中缝苍白核表达逐渐减少,中缝背核表达逐渐增加. 结论睡眠剥夺影响 GFAP蛋白的表达, AS参与睡眠调节.