更年期潮热的单胺类神经递质学说

潮热是更年期女性最常见的症状,并且其症状与心血管疾病的发生密切相关,严重影响着更年期女性的身心健康,因此,避免和减轻更年期潮热的发生已经成为当今倍受关注的课题。目前,普遍认为潮热是由下丘脑体温调节中枢功能紊乱所致,但其确切的发病机制尚未阐明。最近的研究相继表明,更年期潮热是雌激素与多种神经递质交互作用的结果,其中单胺类神经递质去甲肾上腺素、5 羟色胺和多巴胺等起到了核心作用,现将其综述如下。     

单胺类神经递质及其受体在抑郁症免疫失衡中的作用

目前认为抑郁症发病机制是由于中枢单胺类递质5-羟色胺,去甲肾上腺素和多巴胺等特定的神经递质的含量及其受体功能异常所致.抑郁症同时并存各种躯体疾病相关的免疫改变:在抑郁症患者中可以发现相对正常人群其促炎症因子的表达上升,抗炎症因子的表达下降;Th1/Th2和Th1/Th3的比率增高.单胺类递质及其受体不仅存在于中枢系统,在免疫系统中也广泛分布,B细胞、T细胞、单核细胞和巨噬细胞上均可见到单胺类递质受体.单胺类神经递质和内分泌系统及某些细胞因子之间存在复杂的联系,抑郁症患者不仅可以使促炎症细胞因子/抗炎症细胞因子的比率发生变化,引起不同淋巴细胞亚型的变化,同时也存在着内分泌系统的变化,通过神经递质-内分泌-免疫网络,神经递质在抑郁症免疫失衡中发挥着重要的调节作用.     

启神胶囊对全脑反复缺血再灌注大鼠脑内单胺类神经递质含量的影响

为了探讨启神胶囊对全脑反复缺血再灌注大鼠脑内单胺类神经递质的影响 ,Wister大鼠 ,采用 4-血管反复缺血再灌注造模 ,分正常对照组、模型组、模型喂药组 ,30天后取脑 ,用HPLC—ECD法测定 ,结果表明 ,模型大鼠海马组织中NE、MHPG、5—HT含量下降 ,与正常对照组差异显著 (p <0 .0 5 ) ;中药组大鼠海马组织中NE、MHPG、5—HT、HVA比模型鼠显著上升 (p <0 .0 5 )。模型大鼠大脑皮层中NE、MHPG、DA、HVA含量明显低于对照组 ,中药组NE、HVA含量均比模型组显著提高 (p <0 .0 5 ) ;MHPG、DA虽也有提高 ,但无统计学差异 ;5—HT含量 ,模型组高于对照组 (p <0 0 5 ) ,中药组低于模型组 (p <0 .0 5 )。启神胶囊能影响全脑缺血再灌注大鼠单胺类神经递质的代谢     

安神方对大鼠抑郁模型行为学及单胺类神经递质的影响

目的探讨中药复方安神方抗抑郁作用的机制。方法以慢性中等强度应激刺激建立大鼠抑郁模型,用强迫游泳试验进行行为学评分,用高效液相电化学检测方法检测大鼠脑干内单胺类神经递质的含量,观察模型大鼠给药前后的变化。结果抑郁模型大鼠第7天与第28天水中强迫游泳不动时间分别为（133.4±24.0）s、（179.7±35.3）s,正常组则为（127.9±31.3）s、（131.8±29.3）s,模型组显著高于正常组（P〈0.05）;脑干内5-HT、NE含量显著降低,模型组为（0.093±0.031）ng/mg、（0.146±0.038）ng/mg,正常组为（0.160±0.023）ng/mg、（0.237±0.049）ng/mg（P〈0.05）;安神方高剂量组第7天与第28天水中强迫游泳不动时间分别为（121.5±27.8）s、（145.1±24.2）s,与模型组比较显著降低（P〈0.05）,大鼠脑干内5-HT、NE含量分别为（0.151±0.021）ng/mg、（0.208±0.057）ng/mg,较正常组显著提高（P〈0.05）。结论安神方具有抗抑郁作用,对中枢单胺类神经递质的调节作用是其疗效机制之一。     

氯氮平对局灶性脑缺血再灌注大鼠脑内单胺类神经递质含量的影响

观察氯氮平对大鼠局灶性脑缺血再灌注单胺类神经递质变化与组织病理学改变的影响，探讨氯氮平对缺血再灌注损伤的保护作用及其机制。采用线栓法制作大鼠大脑中动脉局灶性脑缺血再灌注模型，用荧光分光光度计测定缺血2h再灌注lh时大脑皮层及纹状体NE、DA、5-HT含量；脑组织切片HE染色，光镜下观察组织病理学变化。结果可见；氯氮平12mg/kg、24mg/kg组能显著提高缺血2h再灌lh时大鼠大脑皮层及纹状体NE、DA、5-HT含量，并能显著改善间质脑水肿。表明氯氮平对脑缺血再灌注损伤有保护作用，其作用机制可能与减少缺血再灌注期间单胺类神经递质的释放有关。     

航天特定环境下抑郁症模型大鼠血清、海马及延髓中单胺神经递质含量变化

目的 研究航天特定环境下抑郁症模型大鼠血清、海马及延髓中单胺神经递质的变化.方法 选择旷场实验行为学评分相近的30只大鼠,按完全随机法分为对照组和模型组,每组15只.模型组采用经典抑郁症模型,结合航天特定环境,建立大鼠抑郁症模型,对照组不做任何处理.观察航天特定环境下抑郁症模型大鼠行为学变化,测定血清、海马、延髓组织中5-羟色胺(5-HT)、多巴胺(DA)及去甲肾上腺素(NE)含量的变化.结果 与对照组比较,造模后模型组大鼠旷场实验中的穿行格数和直立次数减少,理毛次数、中央格停留时间增加(均P＜0.05);模型组大鼠血清中5-HT、DA及NE含量均高于对照组[(334.23±110.45)μg/L比(248.76±51.83)μg/L,(109.19±26.86)μg/L比(88.42±12.63)μg/L,(102.46±39.31)μg/L比(74.88±12.04)μg/L,均P＜0.05)],而海马组织中NE含量低于对照组[(9.99±8.02)μg/L比(25.41±5.68)μg/L,P＜0.05].结论 航天抑郁症的产生可能与血清中5-HT、DA降低无关,而与海马组织中的NE降低有关.     

切除卵巢大鼠脑内单胺类含量及应激的影响

本文观察了切除卵巢（ＯＶＸ）大鼠脑内单胺类含量的变变以及应激对这些变化的影响。结果：ＯＶＸ鼠血清雌激素水平明显下降，睾酮含量不变，体重呈明显上升趋势。在应激条件下，正常鼠下丘脑去甲肾上腺素（ＮＥ）含量不变，ＯＶＸ鼠明显下降。应激使正常鼠纹状体多巴胺（ＤＡ）含量明显下降，其水平与未应激的ＯＶＳ鼠相同，而ＯＶＳ鼠于应激前后无明显改变。提示雌激素撤退有可能改变机体对应激的反应性和适应性。     

航天特定环境下抑郁症模型大鼠血清、海马及延髓中单胺神经递质含量变化

Objective To explore the changes of monoamine neurotransmitters in serum,hippocampus and medulla oblongata of experimental depression rats under simulated space-specific environment. Methods Thirty rats with similar behavior scores at open field test were randomized into model group and control group (n=15 each). Classical pattern of depression combined with simulated spacespecific environment was used to establish the rat models of depression in the model group, whereas the rats in the control group received no treatment. Under simulated space-specific environment, the changes of behavior were observed and the changes of neurotransmitters including 5 - hydroxytryptamine (5 - HT) ,dopamine (DA) and norepinephrine (NE) in serum, hippocampus and medulla oblongata were measured.Results Compared with controls, the depressed rats walked through fewer squares, experienced less upright actions, more grooming and time at the central square (all P＜ 0.05). In the model rats, the serum contents of 5-HT [ (334.23±110.45)μg/L vs (248.76±51.83)μg/L], DA [ (109.19±26.86) μg/L vs (88.42±12.63) μg/L] and NE [ ( 102.46±39.31 ) μg/L vs (74.88±12.04) ] were significantly elevated (all P＜0.05),and NE [ (9.99±8.02) μg/L vs (25.41±5.68)μg/L,P＜0.05] in hippocampus was reduced, as compared with controls. Conclusion The major cause of space environment-related depression may be associated with the reduced level of NE in hippocampus and not associated with the reduced levels of 5-HT and DA in serum.     

针灸对围绝经期抑郁症单胺类神经递质影响的关联性研究

单胺类神经递质属于中枢神经递质,是一类生物学活性比较广泛的物质,单胺类神经递质含量的平衡失调与围绝经期抑郁症的发病密切相关。中医针灸治疗围绝经期抑郁症已取得很好的疗效,同时对单胺类神经递质具有调节作用,本文通过研究针灸、围绝经期抑郁症以及单胺类神经递质三者之间的关联性,进一步明确中医针灸治疗围绝经期抑郁症可能的机制之一,为临床治疗提供理论依据。     

The effect of hypoxia on monoamine levels in discrete regions of aged rat brain

Aged rats were exposed to 10% oxygen for 2, 13, and 36 hr. Norepinephrine levels in cerebral cortex, hypothalamus, hippocampus, midbrain, cerebellum, ponsmedulla and dopamine levels in striatum were determined after each exposure. While there was no significant change in monoamine levels in brain regions after 2 hr, norepinephrine concentration in hypothalamus and midbrain decreased significantly after 13 hr of hypoxia. After 36 hr in a hypoxic environment, levels of the monoamines in brain regions were similar to the controls. This would suggest NE metabolism is most vulnerable to hypoxia in two regions of the aged brain. The precise mechanism of these changes is unknown, but they suggest both a vulnerability and an adaptive recovery of central adrenergic metabolism by the aged brain under hypoxia.     

甘丙肽和经典神经递质在大鼠和家兔背根神经节细胞内共存的免疫组织化学研究

为研究背根神经节细胞内生物活性物质间的关系，用免疫组织化学ＡＢＣ法，证实大鼠和家兔背根神经节存在甘丙肽免疫阳性反应细胞。用相邻镜像邻片免疫双标记技术，观察到甘丙肽分别与５－ＨＴ和ＤＡ在家兔和大鼠背根神经节细胞内共存。此结果为进一步研究背根神经节细胞内生物活性物质间的关系提供了形态学资料。     

Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects

Therapeutic response to theophylline in asthma is generally attributed to its effect in increasing intracellular 3′,5′ cyclic adenosine monophosphate (cAMP) by competitive inhibition of cAMP phosphodiesterase. However, because of discrepancies between therapeutic serum theophylline concentration achieved clinically and those required for in vitro phosphodiesterase inhibition, we explored the possibility that theophylline may act through adrenomedullary secretion of catecholamines. Five healthy, nonasthmatic male and female adults were studied with a double-blind, randomized, crossover protocol. Theophylline (5 mg/kg) and placebo were administered in a capsule dosage form. Plasma catecholamines epinephrine (E), norepinephrine (NE), and dopamine (DA) were measured by a radioenzymatic assay at baseline and after administration of theophylline at 1, 2, and 3 hr. Significant differences between theophylline- and placebo-treated groups (p < 0.05) were seen at 3 hr for mean percentage increase over baseline with E (120% ± 25.3%) and NE (48.02% ± 17.94%) after theophylline therapy (mean peak level 7.2 ± 0.48 μg/ml). Epinephrine plasma concentration was significantly greater (p < 0.001) at 3 hr compared with baseline (105 ± 16 vs 56 ± 18 pg/ml), while NE (448 ± 52 vs 320 ± 36 pg/ml) did not attain significance (p = 0.136). A significant correlation (p < 0.05) was found between the percentage increase over basal for E (r = 0.58) and NE (r = 0.66) and serum theophylline levels. DA was not significantly increased at any time period. Thus theophylline in clinically relevant concentration appears to stimulate adrenomedullary secretion of catecholamine. Whether this is an important mechanism of action in asthma or explains some side effects of theophylline remains to be determined.     

Persisting effects on adult brain monoamines of neonatal distress and carbon monoxide exposure

Perinatal factors causing distress or trauma to the neonate are often linked to behavioral abnormalities in development and later life; however, little is known of the long-term effects of these experiences on neurotransmitter systems. This study used carbon monoxide exposure to produce a slow onset and recovery hypoxic episode of two hours in 5-day-old rat pups. This required placement of the pups in a hypothermic environment (air exposure) isolated from the dam so the effects of this distressing experience were also studied. When the brains of these animals were assayed at adulthood, air exposure was found to have increased dopamine and reduced 5-hydroxytryptamine levels in the frontal cortex. Norepinephrine levels were reduced in both midbrain and pons-medulla but the 5-hydroxytryptamine level was increased in midbrain. Hypoxia, induced with carbon monoxide, prevented changes in 5-hydroxytryptamine levels in cortex and brain stem and modified effects on norepinephrine. However, hypoxia resulted in significant decreases in striatal dopamine levels accompanied in females by increased norepinephrine and 5-hydroxytryptamine levels. The data reported here indicate that neonatal distress can have considerable impact on developing neurotransmitter systems. Furthermore, brain region and sex influence the outcome. Carbon monoxide-induced hypoxia, under the same conditions, produced a different pattern of change with particular predeliction for the striatum. Again there were regional and sex differences in the neurotransmitter effects. It is concluded that this hypoxic model may be valuable in the study of developmental disorders.     

Simultaneous determination of indole- and catecholamines in small brain regions in the rat using a weak cation exchange resin

A fluorometric procedure is described which allows the measurement of nanogram amounts of serotonin, horepinephrine, and dopamine in small brain areas (20–350 mg) from individual rats. The amines are separated from their precursor amino acids and acid metabolites by a single-column chromotography step using a weak cation exchange resin. It is possible quantitatively to determine 10–30 ng of each amine when all three are measured simultaneously. When either serotonin or the catecholamines are assayed in a tissue sample, as little as 5–15 ng may be detected. Recoveries of the amines range from 85 to 93% as measured by addition of¹⁴C-labeled amines to tissue supernatants.     

Sex-dependent maternal deprivation effects on brain monoamine content in adolescent rats

Rats subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal days 9–10] show, later in life, behavioural alterations that resemble specific signs of schizophrenia and other neuropsychiatric signs including increased levels of impulsivity and an apparent difficulty to cope with stressful situations. Some of these behavioural modifications are observable in the periadolescent period. However there is no previous information regarding the possible underlying neurochemical correlates at this critical developmental period. In this study we have addressed the effects of MD on the levels of serotonin (5-HT), dopamine (DA) and their respective metabolites in prefrontal cortex, hippocampus, striatum, midbrain and cerebellum of male and female periadolescent Wistar rats. MD rats showed significantly increased levels of 5-HT in all regions studied with the exception of cerebellum. In addition, MD animals showed increased levels of DA in PFC as well as increased levels of DA and a decrease of DOPAC/DA and HVA/DA ratios in striatum. The effect of MD on the monoaminergic systems was in several cases sex-dependent.     

Age-related changes in Pavlovian conditioning: central nervous system correlates

Two groups of New Zealand Albino rabbits, average age 6 and 40 months, were subjected to Pavlovian conditioning in which eyeblink (EB) and heart rate (HR) responses were assessed. At the end of conditioning biogenic amine content was assessed in several brain areas; dopamine receptor binding was assessed in caudate nucleus. Older animals revealed an impairment in EB conditioning relative to the young animals; the conditioned decelerative HR response was increased in magnitude in the old animals. Significant deficits in cortical norepinephrine and serotonin were observed in the old subjects, but in both old and young animals the magnitude of the bradycardia was positively correlated with forebrain norepinephrine and inversely correlated with serotonin concentration. Receptor binding experiments revealed that 3H-spiroperidol receptor density was decreased in caudate nuclei of old animals; however, receptor affinity was unaffected by age.     

海马去甲肾上腺素能及乙酰胆碱能系统损伤对大鼠类P3的影响

目的:借助P300研究在不同神经递质缺失状态下认知功能的改变。方法:手术切断大鼠左侧穹窿海马伞(FF)建立胆碱能系统损伤模型,向大鼠双侧背去甲肾上腺素束注射6-OHDA建立去甲肾上腺素能系统损伤模型,于建模前后对其进行迷宫检查及类P3潜伏期测定。结果:两种神经递质系统的失常均可造成大鼠类P3潜伏期显著长于对照组,并与迷宫测试指标(EN、TRT)成正相关关系,但在两个实验组之间未见有显著差异。结论:乙酰胆碱与去甲肾上腺素在P300的产生与整合机制中均占有重要地位。