Thy1.1干细胞对损伤动脉一氧化氮合成酶的影响

背景：目前干细胞移植对血管成形后再狭窄的影响存在争议。 目的：观察大鼠Thy-1.1干细胞局部移植对大鼠颈总动脉球囊损伤后内膜增生的影响,探讨干细胞移植对内皮型一氧化氮合成酶及诱生型一氧化氮合成酶的影响,并评价干细胞移植对再狭窄的影响与一氧化氮合成酶的关系。 方法：4~6周龄雄性SD大鼠用于制备骨髓Thy-1.1干细胞。雌性SD大鼠随机抽签法法分为3组,干细胞组：于颈总动脉球囊损伤后即刻将约5×106 Thy-1.1干细胞注入至损伤血管局部;损伤组：颈总动脉球囊损伤后局部注入等量生理盐水;对照组：与损伤组共用大鼠,损伤组取材左侧损伤颈总动脉,对照组取右侧未损伤颈总动脉。各组各于术后即刻、3,7,14,21,28 d麻醉并处死大鼠,留取两侧颈总动脉标本。应用组织形态学方法检测内膜增生并进行计算机图像分析,RT-PCR方法检测内皮型一氧化氮合成酶及诱生型一氧化氮合成酶的表达情况。 结果与结论：①干细胞组内膜面积低于损伤组(P < 0.05)。②损伤组内皮型一氧化氮合成酶mRNA明显低于对照组,诱生型一氧化氮合成酶mRNA表达高于对照组(P < 0.05)。③干细胞组内皮型一氧化氮合成酶mRNA及诱生型一氧化氮合成酶mRNA表达均明显高于损伤组(P < 0.05)。提示Thy-1.1干细胞局部移植可抑制内膜增生,对球囊损伤具有修复作用,这可能与Thy-1.1干细胞增加一氧化氮合成酶的表达,促进大鼠颈总动脉球囊损伤后再内皮化有关。     

外周血内皮祖细胞数量变化与颅内动脉瘤的生成

背景：动脉内膜损伤是动脉瘤发生的始动因素,内皮祖细胞能修复受损的动脉内膜。 目的：建立大鼠颅内动脉瘤模型,探讨动脉瘤大鼠内皮祖细胞数量变化及意义。 方法：40只SD大鼠随机分为两组,正常组作为正常对照,不给予任何干预。模型组大鼠手术结扎双侧肾动脉后支以及左侧颈总动脉,术后喂食含8%氯化钠鼠粮。于2周,1,2,3个月末测量大鼠内皮祖细胞变化,并与3个月末测量各组大鼠血压及动脉瘤大小,RT-PCR检测willis环相关基因表达。 结果与结论：模型组大鼠内皮祖细胞数目于2周后就开始下降,与正常组比较差异有显著性意义(P < 0.05),一直持续到3个月末(P < 0.01)。模型组大鼠动脉瘤壁基质金属蛋白酶9表达明显高于正常组正常大鼠(P < 0.01),而内皮型一氧化氮合酶明显低于正常(P < 0.05)。结果提示循环内皮祖细胞数量降低可能是动脉瘤生成的一个重要因素。     

肾性高血压大鼠脑血管病理及发病机制的研究

目的　探讨肾性高血压大鼠高血压形成的可能机制 ,观察脑内大动脉和血液流变学改变的特点。方法　比较 14周后的肾性高血压大鼠 (实验组 )与对照组大脑中动脉和基底动脉的血管变化 ,并检测血液中降钙素基因相关肽 (CGRP)、内皮素 (ET) ,观察血液流变学变化及脑组织c sis基因表达量。结果　实验组大鼠的大脑中动脉平滑肌增厚、血管横切面积、中层面积、管腔面积增大 ;基底动脉平滑肌增厚、中层面积增大 ,血管横切面积、管腔面积变窄。血液粘度增高 ,血浆内皮素 (ET)、降钙素基因相关肽 (CGRP)水平、c sis基因表达量与对照组有极显著差异。结论　肾动脉狭窄可引起大鼠大脑中动脉、基底动脉血管重构 ,血液粘度增高以及血浆ET、CGRP合成、分泌不平衡 ;c sis基因表达增多等这些变化都可能是导致动脉硬化的重要因素。     

失神经固定制动不同时间大鼠降钙素基因相关肽水平变化对骨密度的影响*

背景：大量研究认为降钙素基因相关肽具有刺激成骨、增加骨量,促进神经再生等诸多功能,然而不同制动后降钙素基因相关肽的变化规律及对骨质疏松形成过程中的作用和机制至今仍不十分清楚。 目的：观察失神经固定后神经肽物质对大鼠骨密度的影响及其可能机制。 设计、时间及地点：随机对照动物实验,于2006-09/11在湘南学院附属医院完成。 材料：10周龄SD雄性大鼠96只,体质量220~250 g,用于制备失神经支配模型。 方法：96只SD大鼠按数字表法随机分为3批,每批4组,每组8只。失神经支配组：大鼠麻醉后,先于俯卧位行两侧后肢股外侧切口,于股骨转子水平切断双侧坐骨神经;再置大鼠于仰卧位,行两侧股正中纵切口,于腹股沟韧带水平切断大鼠两侧股神经,远端游离5 mm,缝合切口。固定组：大鼠固定与失神经支配手术同时进行,麻醉后应用管型石膏分别固定1,10,30,60 d。对照组行假手术,即在造模过程中仅暴露神经,然后缝合伤口。 主要观察指标：实验期间大鼠的一般情况;造模后1,10,30,60 d各组大鼠胫骨骨密度和降钙素基因相关肽的变化及降钙素基因相关肽水平与骨密度水平相关性。 结果：96只SD大鼠均进入结果分析。①大鼠失神经造模后两后肢无主动屈伸功能,前进时以臀部肌群帮助行走,后退时靠腰腹部肌群收缩代偿,活动量显著减少。固定组大鼠精神好,活动时后肢拖地。对照组大鼠无明显异常。②造模后10,30,60 d失神经支配组大鼠胫骨降钙素基因相关肽的表达低于对照组(P < 0.05~0.01);而固定组仅造模后30 d时与对照组之间存在显著性差异(P < 0.05)。造模后10,60 d固定组高于失神经支配组(P < 0.05~0.01)。③与对照组相比,失神经支配组、固定组造模后30,60 d骨密度降低(P < 0.05~0.01);失神经支配组和固定组造模30 d时骨密度开始下降,60 d后下降明显,组内比较差异有显著性意义(P < 0.05~0.01)。④失神经后降钙素基因相关肽与骨密度水平变化高度相关(P < 0.05);而固定后降钙素基因相关肽与骨密度水平变化相关程度不高。 结论：神经的完整性是降钙素基因相关肽水平维持正常的关键,动态观察降钙素基因相关肽水平变化,可在一定程度上预测失神经性骨质疏松形成、发展。     

眩晕宁对椎基底动脉供血不足患者血清SOD、MDA、血浆内皮素及一氧化氮的影响

目的探讨眩晕宁对椎基底动脉供血不足(vertebrobasilar in sufficiency,VBI)患者血清SOD、MDA及血浆内皮素、一氧化氮的影响。方法用比色法测定健康对照组、对照组、治疗组血清MDA和SOD水平,用放射免疫法测定测定血浆内皮素的变化,一氧化氮(NO)采用硝酸还原法测定。结果与健康对照组比较,对照组、治疗组血清SOD活性降低(P0.05),MDA含量降低(P0.05),一氧化氮(NO)降低(P0.05),血浆内皮素水平升高(P0.01)。应用尼莫地平(ni modip-ine,NIM)治疗的对照组虽能够降低血浆内皮素水平和升高NO,但未见SOD、MDA的变化,眩晕宁治疗组能够回升SOD活性,降低MDA含量,与健康对照组及对照组有明显差别(P0.05,P0.05),与对照组比较,治疗组在降低内皮素(endothe-lin,ET)和升高NO方面疗效更为显著(P0.01)。结论眩晕宁可能通过降低氧化应激反应,降低血浆内皮素和升高NO水平,对椎基底动脉供血不足有治疗作用。     

缺血性脑卒中患者血浆内皮素和血浆降钙素基因相关肽的研究

目的探讨血浆内皮素(ET)和血浆降钙素基因相关肽(CGRP)在缺血性脑卒中损伤过程中的变化.方法应用放射免疫分析法测定血浆ET和CGRP水平.结果脑梗死患者的血浆ET明显高于对照组(P＜0.05～0.01),脑梗死患者血浆CGRP明显低于对照组(P＜0.01).结论 ET和CGRP与缺血性脑血管病的病理改变有密切关系.     

睡眠剥夺小鼠海马中BDNF、IL-4变化的研究

目的探究睡眠剥夺过程中小鼠海马组织内脑源性神经营养因子(brain derived neurotrophic factor,BDNF)、白细胞介素4(Interleukin-4,IL-4)的动态变化及相关性,从而为睡眠剥夺对海马学习记忆功能的影响提供可能的理论依据。方法 (1) 6～8周龄C57BL/6J雄性小鼠随机分为正常对照组(Cage control,CC)、快速眼球运动(REM)睡眠剥夺1 d组(REM sleep deprivation 1 day,SD 1 d)、REM睡眠剥夺2 d组(SD 2 d)、REM睡眠剥夺3 d组(SD 3 d),每组12只小鼠。CC组同笼饲养1 w后于9:00AM灌注处死,SD 1 d组、SD 2 d组、SD 3 d组经睡眠剥夺1 d、2 d和3 d后均于9:00AM灌注处死。(2)采用ELISA方法观察各组小鼠海马组织中BDNF、IL-4的表达水平。结果 (1) ELISA显示SD 1 d组小鼠海马中BDNF、IL-4较CC组表达水平升高,差异具有统计学意义(P值分别为0. 029、0. 001); SD 2 d组BDNF、IL-4较CC组表达无明显差异(P值分别为 0. 5、0. 13); SD 3 d组BDNF、IL-4较CC组表达水平明显降低,差异具有统计学意义(P值均为0. 001)。(2) Pearson相关性分析显示睡眠剥夺过程中小鼠海马中IL-4、BDNF蛋白表达变化呈正相关性,P 0. 001,相关系数r=0. 863。结论睡眠剥夺后BDNF、IL-4表达量的变化可能是睡眠剥夺后造成神经损伤的可能机制之一。     

大鼠松质骨中降钙素基因相关肽在脊髓损伤后的变化

背景：细胞因子异常及神经功能的异常、激素水平的改变均参与了脊髓损伤后骨质疏松的发生，以往对细胞因子及激素改变的研究较多，而对神经异常对骨调节的研究相对较少。 目的：课题创新性地应用血生化与免疫组织化学相结合的方法，观察脊髓损伤后大鼠松质骨中神经多肽降钙素基因相关肽的变化，分析其在脊髓损伤后骨质疏松中的意义。 设计、时间及地点：随机对照动物实验，于2008-09/12在解放军第四军医大学骨科研究所实验室完成。 材料：3月龄SD大鼠48只，体质量为(210±16) g，随机均分为脊髓损伤组与对照组，每组24只。 方法：脊髓损伤组于T10处完全横断脊髓；对照组仅行椎板切除术。 主要观察指标：术后1，3，6 周分批每组随机取8只动物处死。测定血骨特异性碱性磷酸酶、Ⅰ型胶原氨基末端肽；对股骨髁松质骨行降钙素基因相关肽免疫组织化学染色,结合计算机图像分析系统对降钙素基因相关肽免疫阳性神经的染色强度进行定量分析。 结果：脊髓损伤组各时间段血清Ⅰ型胶原氨基末端肽浓度显著高于对照组(P < 0.05或0.01)，各时间段血清骨特异性碱性磷酸酶活性低于对照组，但差异无显著性意义(P > 0.05)。对照组各时间段分布于小梁骨内的降钙素基因相关肽免疫阳性神经呈强阳性，脊髓损伤组降钙素基因相关肽较对照组减弱( P < 0.05或0.01)。 结论：脊髓损伤后松质骨内降钙素基因相关肽的减弱可能与脊髓损伤后骨质疏松的发生有关。     

睡眠剥夺对大鼠脑损害的生化研究

目的 探讨睡眠剥夺(SD)的脑损害机制。方法 采用小平台水环境法建立睡眠SD模型，将30只Sprague-Dawley大鼠随机分为睡眠剥夺1天、3天和5天组(SDld、SD3d、SD5d)，大平台组(TC)和正常对照组(NC)，每组6只。测定脑组织一氧化氮(N0)含量和超氧化物歧化酶(SOD)活性，测定血清髓鞘碱性蛋白(MBP)、皮质醇、白细胞介素—1β(IL-1β)和白细胞介素—2(IL—2)含量。结果 (1)N0含量：SD各组及TC组鼠额叶、海马和中脑的N0含量均高于NC组(F＝10．97，7．96，5．23，P＜0．01)，且随SD时间的延长而升高；仅下丘脑N0含量差异未达显著性(F＝1．64，P＞0．05)。(2)SOD活性：SD各组及TC组鼠额叶、海马、中脑和下丘脑SOD活性均高于NC组(F＝10．44，16．15，28．94，12．75，P＜0．01);其中在海马、中脑和下丘脑SOD活性均以SD3组为最高。(3)血清皮质醇、IL-1β、IL—2和MBP含量：SD各组均高于NC组(F＝8．60，3．62，3．84，2．83，P＜0．01和P＜0．05)，且各项指标含量均随SD时间的延长而逐渐升高。TC组仅皮质醇的含量与NC组的差异有显著性。结论 睡眠剥夺的脑损害可能与N0、氧自由基、皮质醇及细胞因子等生化因素有关。     

高原环境对睡眠剥夺大鼠学习记忆的影响

目的探讨高原环境对睡眠剥夺(SD)大鼠学习记忆及海马5-HT表达的影响。方法64只大鼠被随机分为可可西里组(海拔4767m)和兰州组(海拔1520m)。各组大鼠又分为正常睡眠及SD1d、3d和5d4个亚组。采用小平台水环境法(flowerpot)建立大鼠SD模型。各组大鼠行Morris水迷宫测试,免疫组化法检测海马组织中5-HT的含量。结果Morris水迷宫显示,在可可西里组和兰州组中,与正常睡眠大鼠比较SD1d、3d及5d大鼠的潜伏期延长(P0.05),游泳路程增加(P0.05);以及穿越平台次数减少(P0.05)。与兰州组比较,可可西里组的正常睡眠及SD1d、3d和5d大鼠的潜伏期延长(P0.05),游泳路程增加(P0.05),穿越平台次数减少(P0.05或P0.01)。海马5-HT含量检测中可可西里组SD1d、3d及5d大鼠的含量均高于正常睡眠大鼠(P0.05);兰州组SD3d及5d大鼠的含量均高于正常睡眠大鼠(P0.05);与兰州组相比,可可西里组正常睡眠、SD1d、3d和5d大鼠的5-HT含量增加(P0.05)。结论高原环境暴露可使SD大鼠学习记忆能力进一步降低,其机制可能与海马中5-HT含量增高有关。     

Distinct behavioral and neurochemical alterations induced by intermittent hypoxia or paradoxical sleep deprivation in rats

The current study investigated the effects of paradoxical sleep deprivation and intermittent hypoxia by examining whether a combination of the two would induce anxiety-like alterations in behavior. The neurochemical effects of these manipulations were investigated by measuring cortical, striatal and hippocampal monoamine concentrations. Wistar Hannover rats were submitted to subchronic (3 days) intermittent hypoxia exposure (alternating cycles of 2 min room air-2 min 10% O2 from 0700-1900 h) and paradoxical sleep deprivation using the single platform method. Rats were randomly assigned to four different protocols: 1) control, 2) intermittent hypoxia during the light period (12 h/day), 3) paradoxical sleep deprivation (24 h/day), and 4) intermittent hypoxia combined with paradoxical sleep deprivation. Rats subjected to intermittent hypoxia showed no modification in the behavioral or neurochemical parameters assessed. Although paradoxical sleep deprivation did not produce alterations in anxiety-like behavior, the rats did increase exploratory activity in the elevated plus-maze. Moreover, a significant increase in striatal epinephrine and hippocampal homovanilic acid (HVA) concentrations was found in the paradoxical sleep deprivation groups, but not in the intermittent hypoxia/paradoxical sleep deprivation group. Of note, both paradoxical sleep deprivation and intermittent hypoxia/paradoxical sleep deprivation groups showed an increase in plasma corticosterone concentration. These results suggest that paradoxical sleep deprivation induces behavioral alterations, and these abnormalities may reflect altered neurotransmission in the brain. When paradoxical sleep deprivation was combined with intermittent oxygen depletion, the behavioral and biochemical parameters were comparable to those of control rats.     

Intermittent hypoxia and sleep restriction: motor, cognitive and neurochemical alterations in rats

The present study evaluated the effects of intermittent hypoxia (IH) and sleep restriction (SR) upon motor and cognitive function in rats. Also evaluated were catecholamine concentrations and tyrosine hydroxylase (TH) protein expression in different regions of the forebrain. Wistar Hannover rats were submitted to IH for 4 days or 21 days (2 min room air to 2 min 10% O(2) for 10:00-16:00 h), followed by SR for 18 h (16:00-10:00 h). Rats were randomly assigned into four experimental groups: (1) control (2) IH (3) SR and (4) IH-SR. In the inhibitory avoidance task, an additional group of rats was submitted to paradoxical sleep deprivation (PSD) for 96 consecutive hours. Results showed that SR induced an increase in motor activity without modifying catecholaminergic turnover in the frontal cortex and striatum. The increase in exploratory activity in SR rats could be the result of impaired habituation. Neither SR periods induced cognitive deficits in the inhibitory avoidance task after 5 or 21 days. However, 96 h of PSD impaired acquisition/retention in rats. Exposure to IH did not affect motor and cognitive function but IH was associated with SR in increased motor activity. After 21 days, IH and IH-SR reduced striatal norepinephrine concentration although neither SR nor IH affected TH protein expression. The results presented here suggest that hypoxia and sleep loss exert distinct deleterious effects upon the central nervous system.     

Effect of acute total sleep deprivation on plasma melatonin,cortisol and metabolite rhythms in females

Disruption to sleep and circadian rhythms can impact on metabolism. The study aimed to investigate the effect of acute sleep deprivation on plasma melatonin, cortisol and metabolites, to increase understanding of the metabolic pathways involved in sleep/wake regulation processes. Twelve healthy young female participants remained in controlled laboratory conditions for ~92 hr with respect to posture, meals and environmental light (18:00–23:00 hr and 07:00‐09:00 hr <8 lux; 23:00–07:00 hr 0 lux (sleep opportunity) or <8 lux (continuous wakefulness); 09:00–18:00 hr ~90 lux). Regular blood samples were collected for 70 hr for plasma melatonin and cortisol, and targeted liquid chromatography–mass spectrometry metabolomics. Timepoints between 00:00 and 06:00 hr for day 1 (baseline sleep), day 2 (sleep deprivation) and day 3 (recovery sleep) were analysed. Cosinor analysis and MetaCycle analysis were performed for detection of rhythmicity. Night‐time melatonin levels were significantly increased during sleep deprivation and returned to baseline levels during recovery sleep. No significant differences were observed in cortisol levels. Of 130 plasma metabolites quantified, 41 metabolites were significantly altered across the study nights, with the majority decreasing during sleep deprivation, most notably phosphatidylcholines. In cosinor analysis, 58 metabolites maintained their rhythmicity across the study days, with the majority showing a phase advance during acute sleep deprivation. This observation differs to that previously reported for males. Our study is the first of metabolic profiling in females during sleep deprivation and recovery sleep, and offers a novel view of human sleep/wake regulation and sex differences.     

Differential sympathetic activation induced by intermittent hypoxia and sleep loss in rats: Action of angiotensin (1-7)

The present study attempted to evaluate the effects of chronic intermittent hypoxia (CIH) associated with sleep restriction in hemodynamic parameters and the plasma renin-angiotensin system. Wistar-Hannover rats were submitted to isolated CIH exposure (1000-1600 h), sleep restriction (1600-1000 h), defined as 18-h paradoxical sleep deprivation followed by 6-h sleep permission period and CIH associated to sleep restriction for 21 days. The CIH and sleep restriction group showed a preferential increase in renal sympathetic nervous system (rSNA) associated with a reduction in plasma angiotensin (1-7) concentrations. However, CIH-sleep restriction rats did not modify rSNA and showed a higher angiotensin (1-7) concentration when compared to isolated CIH and sleep restriction. These results suggest that CIH and sleep restriction impaired the cardiovascular system, and its association to sleep loss can modify these effects by partially restoring circulating angiotensin (1-7).     

Nitric oxide synthase and intermittent hypoxia-induced spatial learning deficits in the rat

Intermittent hypoxia (IH) during sleep induces significant neurobehavioral deficits in the rat. Since nitric oxide (NO) has been implicated in ischemia-reperfusion-related pathophysiological consequences, the temporal effects of IH (alternating 21% and 10% O(2) every 90 s) and sustained hypoxia (SH; 10% O(2)) during sleep for up to 14 days on the induction of nitric oxide synthase (NOS) isoforms in the brain were examined in the cortex of Sprague-Dawley rats. No significant changes of endothelial NOS (eNOS) and neuronal NOS (nNOS) occurred over time with either IH or SH. Similarly, inducible NOS (iNOS) was not affected by SH. However, increased expression and activity of iNOS were observed on days 1 and 3 of IH (P < 0.01 vs. control; n = 12/group) and were followed by a return to basal levels on days 7 and 14. Furthermore, IH-mediated neurobehavioral deficits in the water maze were significantly attenuated in iNOS knockout mice. We conclude that IH is associated with a time-dependent induction of iNOS and that the increased expression of iNOS may play a critical role in the early pathophysiological events leading to IH-mediated neurobehavioral deficits.     

Oculomotor impairment after 1 night of total sleep deprivation: a dissociation between measures of speed and accuracy.

OBJECTIVES: The present study examined the effects of 40 h of sleep deprivation and of time-of-day on saccadic and smooth pursuit oculomotor performance. METHODS: Nine normal subjects slept for 3 consecutive nights in the laboratory (one adaptation, one baseline, one recovery). Baseline and recovery were separated by a period of 40 h of continuous wakefulness, during which subjects were tested every 2 h. Oculomotor performance assessed at the following hours: 10:00, 12:00, 14:00, 16:00, 18:00, 20:00, 22:00, of both the days preceding and following the sleep deprivation night, as well as at 24:00, 02:00, 04:00, 06:00 and 08:00 h during the deprivation period. RESULTS: Saccade latency increased and peak velocity decreased significantly during the post-deprivation day; saccadic accuracy was unaffected. As regards smooth pursuit performance, phase (a measure of accuracy) was not affected by sleep loss, while velocity gain significantly decreased during the day that followed the sleep deprivation night. Significant time-of-day effects on the considered oculomotor variables except saccadic accuracy were also found, indicating an overall performance impairment during the night. CONCLUSIONS: It is concluded that 40 h of sleep deprivation significantly impaired diurnal performance in pursuit and saccadic tasks. This performance worsening is limited to the measures of speed, while accuracy is not affected by sleep loss. A significant operational relevance of these results is suggested, since saccadic velocity has recently been found to be negatively correlated with simulator vehicle crash rates.     

快速动眼睡眠剥夺对大鼠学习、记忆能力及海马组织自噬的影响

目的 探讨快速动眼(rapid eye movement,REM)睡眠剥夺后与大鼠认知相关的行为学变化及脑内海马组织中自噬相关蛋白的表达水平。方法 健康成年雄性大鼠经过筛选后分为空白对照组(CC组)、环境对照组(TC组)、睡眠剥夺组(SD组),每组各6只; 采用改良多平台睡眠剥夺法(modified multiple platform method,MMPM)建立睡眠剥夺模型,连续剥夺5 d后利用Morris水迷宫检测大鼠认知功能; 用蛋白质印记法(Western Blot,WB)检测自噬相关微管蛋白(LC3)及SQSTM1/P62的表达水平变化。结果 与CC组和TC组比较,SD组大鼠毛色无光泽、易激惹、体重下降(P<0.05)。SD组与其他2组比较,逃逸潜伏期延长、目标象限时间减少(P<0.05)。WB显示SD组与其他2组比较,大鼠脑内海马组织自噬相关蛋白LC3-II表达水平上升,P62水平下降(P<0.05)。CC组与TC组大鼠比较,体重、学习记忆能力、海马组织自噬蛋白表达水平均无明显差异(P>0.05)。结论 睡眠剥夺后可损害大鼠学习及记忆功能,海马组织中自噬水平上调提示自噬活动可能参与睡眠剥夺介导的认知功能障碍过程。     

腹膜透析液添加尿激酶对尿毒症合并急性脑梗死患者治疗机理研究

目的探讨腹膜透析液添加尿激酶对尿毒症并发脑梗死患者血清超氧化物歧化酶(SOD)、丙二醛(MDA)、血浆内皮素(ET)及一氧化氮(NO)的影响。方法将健康体检者30人设为健康组,60例尿毒症并发脑梗死患者随机分为治疗组(30例)和观察组(30例),两组基础治疗相同,治疗组在观察组基础治疗上加用腹膜透析液添加尿激酶,治疗8w后观察两组患者超氧化物歧化酶、丙二醛、内皮素及一氧化氮的变化。用比色法测定健康组、观察组、治疗组血清MDA和SOD水平,用放射免疫法测定血浆ET的变化,NO采用硝酸还原法测定。结果与健康组比较,观察组、治疗组血清SOD活性降低(P<0.05),NO降低(P<0.05),MDA含量升高(P<0.05),血浆ET水平升高(P<0.01)。观察组虽能够降低血浆ET水平和升高NO,但未见SOD、MDA的变化,治疗组能够回升SOD活性,降低MDA含量,与健康组及观察组有明显差别(P<0.05,P<0.05),与观察组比较,治疗组在降低ET和升高NO方面疗效更为显著(P<0.01)。结论腹膜透析液添加尿激酶可能通过降低氧化应激反应,降低血浆ET和升高NO水平,对30例尿毒症并发脑梗死患者有治疗作用。     

Chronic stress during paradoxical sleep deprivation increases paradoxical sleep rebound: association with prolactin plasma levels and brain serotonin content

Previous studies suggest that stress associated to sleep deprivation methods can affect the expression of sleep rebound. In order to examine this association and possible mechanisms, rats were exposed to footshock stress during or immediately after a 96-h period of paradoxical sleep deprivation (PSD) and their sleep and heart rate were recorded. Control rats (maintained in individual home cages) and paradoxical sleep-deprived (PS-deprived) rats were distributed in three conditions (1) no footshock - NF; (2) single footshock - SFS: one single footshock session at the end of the PSD period (6-8 shocks per minute; 100ms; 2mA; for 40min); and (3) multiple footshock - MFS: footshock sessions with the same characteristics as described above, twice a day throughout PSD (at 7:00h and 19:00h) and one extra session before the recovery period. After PSD, animals were allowed to sleep freely for 72h. Additional groups were sacrificed at the end of the sleep deprivation period for blood sampling (ACTH, corticosterone, prolactin and catecholamine levels) and brain harvesting (monoamines and metabolites). Neither SFS nor MFS produced significant alterations in the sleep patterns of control rats. All PS-deprived groups exhibited increased heart rate which could be explained by increased dopaminergic activity in the medulla. As expected, PS deprivation induced rebound of paradoxical sleep in the first day of recovery; however, PSD+MFS group showed the highest rebound (327.3% above the baseline). This group also showed intermediate levels of corticosterone and the highest levels of prolactin, which were positively correlated with the length of PS episodes. Moreover, paradoxical sleep deprivation resulted in elevation of the serotonergic turnover in the hypothalamus, which partly explained the hormonal results, and in the hippocampus, which appears to be related to adaptive responses to stress. The data are discussed in the realm of a prospective importance of paradoxical sleep for processing of traumatic events.     

不同程度睡眠剥夺对大鼠认知和脑线粒体呼吸功能的影响

目的研究不同程度睡眠剥夺对大鼠认知和脑线粒体呼吸功能的影响。方法成年SD大鼠分为5组,分别为对照组(自由睡眠,约每天12 h),每天允许睡眠9 h组,每天允许睡眠6 h组,每天允许睡眠3 h组,全天不睡眠组即0 h组。连续10个实验日,以改良多平台睡眠剥夺法实施睡眠剥夺,以Y-型迷宫测试认知功能,断头处死后以Clark氧电极法测定脑线粒体呼吸功能。结果错误反应次数在各睡眠剥夺组均有显著增加。全天不睡眠组(0 h组)和严重睡眠限制组(3 h组)的每个研究日的错误反应次数与对照组相比,差异均有显著性(P<0.05)。睡眠剥夺各组的呼吸Ⅲ态(state 3 respiration, ST3)耗氧率有明显下降,与对照组相比差异有显著性(P<0.05)。呼吸Ⅳ态(state 4 respiration, ST4)耗氧率,只有全天不睡眠组(0h组)和对照组相比有显著降低(P<0.05)。结论不同程度的睡眠剥夺均会对认知功能及脑线粒体呼吸功能造成不利影响。