老年心肌梗塞后抑郁与5-HT的关系

目的 探讨老年急性心肌梗塞后抑郁与血浆5羟色胺(5-HT)浓度的关系。方法 利用HAMD对抑郁进行评定,同时使用HPLC-EC法检测30例心梗后伴有明显抑郁症状患者的血浆5羟色胺浓度,并与30例不伴明显抑郁症状的患者以及30例健康人进行对照。结果 血浆5-HT含量抑郁组为46.37±24.47(ng/ml),非抑郁组为44.08±13.03(ng/ml),健康对照组为37.01±5.92(ng/ml)。结论　老年急性心肌梗塞患者HAMD与血浆5-HT浓度无相关。     

5-HT能神经通路参与偏头痛的机制研究进展

偏头痛是一种常见的复杂性神经系统疾病。研究证实,下行抑制/易化系统的5-HT能神经通路通过分布在三叉神经血管痛觉通路各级结构上不同亚型的5-HT受体,介导了下行抑制/易化系统中抑制和易化疼痛的双重调痛作用,与偏头痛病理生理机制的形成及治疗密切相关。本文拟对与偏头痛相关的5-HT受体亚型进行综述,以期为临床治疗偏头痛提供新思路。     

高压氧治疗卒中后早发性抑郁的临床初探

目的 早发性抑郁状态是急性卒中患者经常伴发的症状,会影响卒中患者的功能康复.文中旨在评估高压氧对卒中后早发性抑郁状态的治疗作用. 方法 采用汉密尔顿抑郁量表(HAMD)对东部战区总医院2017年6月至2018年7月住院的急性缺血性卒中患者发病1个月后进行抑郁评估,筛选并纳入有早发性抑郁状态的患者.以2018年1月开始实...     

中枢去甲肾上腺素系统在焦虑/抑郁中作用的研究进展

去甲肾上腺素(NE)是一种重要的单胺类神经递质,广泛作用于不同的脑区调控觉醒和应激反射。去甲肾上腺素皮质系统的基本功能是通过对新奇环境刺激和觉醒状态的注意来平衡警醒和观察行为。中枢去甲肾上腺素系统实质与应激反应系统相关,而焦虑和抑郁的发病机制也涉及去甲肾上腺素系统的失调。中枢NE的     

欧前胡素抗抑郁作用及机制研究

目的探讨欧前胡素(IMP)的抗抑郁作用及其机制。方法采用产前束缚应激对孕后期♀鼠建立抑郁模型,将SD♂子代大鼠随机分为5组,每组8只。分别是正常组(CON)、模型组(PS)、阳性组(氟西汀5 mg·kg~(-1)·d~(-1))、IMP低、高剂量组(15、30 mg·kg~(-1)·d~(-1))。均采用灌胃给药,每天1次,连续给药4周。进行糖水偏好、强迫游泳、旷场实验行为学测试,ELISA法、实时定量PCR检测海马及前额叶皮层中5-HT的浓度、5-HTT和5-HT_(1A)R的mRNA表达量。结果 IMP给药4周后,与PS组相比,IMP组糖水偏好度明显上升,不动时间减少,穿越总格子数、穿越中间格子数、直立和理毛次数明显增加(P<0.05,P<0.01),5-HT的浓度及5-HT_(1A)R的mRNA表达明显升高(P<0.05,P<0.01),5-HTT mRNA的表达明显降低(P<0.05,P<0.01)。结论 IMP可明显改善PS♂子代抑郁样行为,具有抗抑郁作用,其机制可能与升高5-HT浓度及5-HT1A R mRNA的表达,降低5-HTT mRNA的表达有关。     

肾脏5-羟色胺合成和降解在高血糖诱导肾损伤时的作用研究

糖尿病患者常出现高血糖性肾损伤(hyperglycemic kidney injury,HKI)并发症.本文研究了高血糖致肾脏5-羟色胺(5-hydroxytryptamine,5-HT)系统表达异常与HKI的关系.动物实验用高脂饲料喂养结合腹腔注射链脲佐菌素建立小鼠2型糖尿病(type 2 diabetes mell...     

超声造影检查在诊断早发性乳腺癌中的效果

目的探讨超声造影检查在诊断早发性乳腺癌中的效果。方法将2014年8月～2017年6月在我院接受治疗的经病理确诊的71例乳腺癌患者按照年龄分为两组,对照组26例患者年龄≤35岁,研究组45例患者年龄 35岁。两组患者均给予常规超声检查及超声造影检查,将两组患者声像图特征进行比较。结果研究组患者病灶横径、造影后横径、纵横比、横径差值与对照组比较差异有统计学意义(P 0.05),两组患者纵径比较差异无统计学意义(P0.05)。两组患者在边界、形态、毛刺征或蟹足征、钙化灶、血流分级、造影剂增强分布、血管分布情况、充盈缺损方面比较差异无统计学意义(P 0.05),研究组相较对照组而言,后方回声衰减少、内部回声不均匀多、高回声晕少、快进快退多、造影剂无滞留少,两组间比较差异有统计学意义(P 0.05)。结论超声造影检查在早发性乳腺癌诊断具有很好的效果,对筛查年轻女性乳腺癌具有重要意义,值得在临床上推广使用。     

褪黑素在早发性卵巢功能不全中的应用及研究进展

早发性卵巢功能不全是一种严重影响女性生育力和生活质量的疾病,多数发病原因不明,治疗手段有限。褪黑素是松果体产生的一种激素,具有调节昼夜节律、睡眠觉醒和抗氧化作用,其水平随着机体衰老而降低。外源性补充褪黑素作为助眠类保健品被广泛使用。研究发现,卵巢组织局部也可合成褪黑素,通过抗氧化应激和调节内分泌等作用保护卵巢功能,褪黑素不足是卵巢衰老的原因之一。该文就外源性补充褪黑素在早发性卵巢功能不全中的应用及研究进展进行综述,并分析了其具体作用机制,以期为早发性卵巢功能不全的治疗提供新的思路与方法。     

炎症因子在早发性卵巢功能不全中的作用机制及中医药治疗研究进展

早发性卵巢功能不全(POI)是常见的妇科内分泌疾病之一。POI的致病因素复杂,发病机制目前尚未明确。随着对POI的深入研究,越来越多的研究者发现炎性细胞因子与POI的发生、发展密切相关。现通过检索近年相关文献,从相关炎症因子角度探讨POI的发病机制,并回顾性分析中医药对POI的治疗,以期为后续的科研及临床工作提供参考。     

5-HT及5-HT3受体在慢性结石性胆囊炎胆囊中的表达

目的 探讨5-羟色胺(5-HT)及5羟色胺3受体(5-HLR)在慢性结石性胆囊炎发病机理中的作用。方法 应用免疫组织化学技术(SP法)检测30例慢性结石性胆囊炎、15例正常对照胆囊组织中5-HT含量及5-HT3受体表达的变化。结果 5HT含量在慢性结石性胆囊炎胆囊粘膜层中高于对照组(P＜0．05),在平滑肌层中无差别。5-HT3受体在慢性结石性胆囊炎平滑肌层中表达低于对照组(P＜0．05)。结论 5-HT及5-HT受体在慢性结石性胆囊炎形成中有一定作用。     

Expression of mRNA for 5-HT2 Receptors and Proteins Related to Inactivation of 5-HT in Mouse Osteoblasts

We analyzed the expression of 5-HT₂ receptors and proteins related to inactivation of 5-HT in primary cultures of mouse osteoblasts. The mRNA for the 5-HT_2A receptor was detectable in anaplastic osteoblasts as well as in differentiated and matured osteoblasts. The mRNA for the 5-HT_2B receptor and 5-HT transporter was undetectable in anaplastic osteoblasts and became detectable in differentiated and matured osteoblasts. It was suggested that 5-HT might regulate the proliferation of anaplastic osteoblasts through the 5-HT_2A receptor without control by 5-HT–inactivating mechanisms. The differentiation and maturation of osteoblasts might be regulated by the activation of the 5-HT_2B receptor under the control of 5-HT inactivation.     

Overview on 5-HT receptors and their role in physiology and pathology of the central nervous system

The present review gives an overview on the serotonin (5-hydroxytryptamine; 5-HT) system, its receptors and their relationship to central nervous system physiology and disorders. Additionally, we also introduce the recent knowledge about the 5-HT receptor ligands in preclinical research, clinical trials and as approved drugs.     

阿戈美拉汀联合坦度螺酮对老年抑郁症患者血清NE、5-HT水平的影响

目的 观察阿戈美拉汀联合坦度螺酮对老年抑郁症患者血清去甲肾上腺素(NE)、五羟色胺(5-HT)的影响,探讨其对抑郁症的临床疗效. 方法 100例抑郁症患者按照随机数字表法分为观察组50例、对照组50例,对照组给予坦度螺酮口服,观察组在对照组基础上加服阿戈美拉汀.治疗前、治疗8周后分别进行汉密尔顿抑郁量表(HAMD)评分,检测血清NE、5-HT表达水平. 结果 治疗前2组患者HAMD评分及血清NE、5-HT水平比较,差异无统计学意义(P>0.05).治疗8周后,观察组比对照组HAMD评分明显降低(P<0.05),血清NE、5-HT水平均明显升高(P<0.05). 结论 阿戈美拉汀联合坦度螺酮可明显升高老年抑郁症患者血清NE、5-HT水平,降低HAMD评分,显著改善抑郁症状.     

The effect of tryptophan on brain 5-HT function: A review

Administration of l-tryptophan (TRP), the amino acid precursor of 5-hydroxytryptamine (5-HT), to animals increases brain 5-HT synthesis and in some circumstances, the release of 5-HT in terminal fields. TRP also appears to increase brain 5-HT neurotransmission in humans because neuroendocrine studies have shown that intravenous TRP produces a dose-related increase in plasma prolactin concentration, probably via indirect stimulation of postsynaptic 5-HT_1A receptors. The effect of TRP on prolactin release in humans is enhanced by several effective antidepressant treatments including tricyclic antidepressants, selective 5-HT re-uptake inhibitors, monoamine oxidase inhibitors and lithium. The ability of these drugs to augment the effect of TRP on brain 5-HT function may represent the pharmacological mechanism that underpins the utility of TRP in combination drug treatments of refractory depression.     

盐酸沙格雷酯对血管系统作用的研究进展

盐酸沙格雷酯(sarpogrelate hydrochloride,安步乐克)是新上市的5-HT 2 受体阻滞剂,其可能通过维持血管内皮细胞完整、防止血管平滑肌细胞增殖等对血管相关疾病具有重要作用.综述近几年来安步乐克对血管系统作用方面的研究,并讨论其作用特点及可能的作用机制.     

Stimulating effect of short term ether anaesthesia on central 5-HT synthesis and utilization in the mouse brain

S. BOURGOIN, Y. MOROT-GAUDRY, J. GLOWINSKI and M. HAMON, Stimulating effect of short term ether anaesthesia on central 5-HT synthesis and utilisation in the mouse brain, European J. Pharmacol 22 (1973) 209–211.Light diethyl ether anaesthesia lasting about 2 min induced a marked acceleration in the rate of turnover of 5-HT in the mouse brain. This was shown by the increase in the accumulation of ³H-5-HT and in the conversion index of tryptophan into 5-HT seen 5 and 10 min after i v. injection of ³H-tryptophan. Endogenous and ³H-tryptophan levels were also maikedly increased in tissues. Therefore, diethyl ether is not an appropriate anaesthestic for use in the study of 5-HT metabolism, even when anaesthesia is induced for short time periods.     

A comparison of the effects on central 5-HT function of sibutramine hydrochloride and other weight-modifying agents

1. Effects on 5-HT function of sibutramine and its active metabolites, BTS 54 354 and BTS 54 505, were compared with fluoxetine, (+)-fenfluramine and (+)-amphetamine.
2. In vitro sibutramine weakly inhibited [³H]-5-HT uptake into brain synaptosomes. BTS 54 354, BTS 54 505 and fluoxetine were powerful [³H]-5-HT uptake inhibitors, whereas (+)-fenfluramine and (+)-amphetamine were very much weaker. Conversely, whilst sibutramine, its metabolites and fluoxetine did not release [³H]-5-HT from brain slices at ?10^?5M, (+)-fenfluramine and (+)-amphetamine concentration-dependently increased [³H]-5-HT release.
3. Sibutramine and fluoxetine had no effect on 5-hydroxytryptophan (5-HTP) accumulation in either frontal cortex or hypothalamus at doses <10 mg kg^?1. In contrast, (+)-amphetamine (?3 mg kg^?1) reduced 5-HTP in hypothalamus, whilst (+)-fenfluramine (?1 mg kg^?1) decreased 5-HTP in both regions.
4. Sibutramine (10 mg kg^?1 i.p.) and fluoxetine (10 mg kg^?1 i.p.) produced slow, prolonged increases of extracellular 5-HT in the anterior hypothalamus. In contrast, (+)-fenfluramine (3 mg kg^?1 i.p.) and (+)-amphetamine (4 mg kg^?1 i.p.) induced rapid, short-lasting increases in extracellular 5-HT.
5. Only (+)-fenfluramine (10 mg kg^?1) altered 5-HT_2A receptors in rat frontal cortex when given for 14 days, producing a 61% reduction in receptor number and a 18% decrease in radioligand affinity.
6. These results show that sibutramine powerfully enhances central 5-HT function via its secondary and primary amine metabolites; this effect, like that of fluoxetine, is almost certainly mediated through 5-HT uptake inhibition. By contrast, (+)-fenfluramine enhances 5-HT function predominantly by increasing 5-HT release. (+)-Amphetamine, though weaker than (+)-fenfluramine, also enhances 5-HT function by release.

     

Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C/2B receptor function

Chronic treatment with selective 5-HT reuptake inhibitors (SSRI) are therapeutic in obsessive compulsive disorder, depression, anxiety, bulimia nervosa and migraine. In the present study the possibility that SSRI's act by desensitizing 5-HT_2C/5-HT_2B receptors was assessed using a putative in vivo model of 5-HT_2C/5-HT_2B receptor function, mCPP-induced hypolocomotion. mCPP (2,4 and 6 mg/kg i.p. 20 min pretest) reduced locomotion and rears in rats treated acutely or chronically with saline. Acute oral administration of the SSRI's fluoxetine (10 mg/kg), paroxetine (10 mg/kg), or clomipramine (70 mg/kg) or the noradrenaline reuptake inhibitor, desipramine (10 mg/kg), all 1 hr pretest, did not prevent mCPP-induced hypolocomotion. In contrast, chronic treatment with the SSRI's paroxetine and fluoxetine (both 10 mg/kg p.o. daily × 21 days), significantly attenuated the effect of mCPP (4 and 6 mg/kg i.p.) on locomotion and rears 24 hr after the last pretreatment dose. Chronic clomipramine (70 mg/kg p.o. daily × 21 days) also significantly attenuated the effect of mCPP (4 mg/kg i.p.) on rears and tended to reduce the hypolocomotor response. However, chronic treatment with desipramine, (10 mg/kg p.o.daily × 21) had no effect on any of the parameters measured. As chronic fluoxetine and paroxetine did not reduce brain mCPP levels (determined by HPLC 30 min after 4 mg/kg i.p.) the results suggest that chronic SSRI's, but not desipramine, reduce 5-HT_2C/5-HT/_2B receptor responsivity. If this occurs in man, it may mediate or contribute to their reported therapeutic efficacy in depression, anxiety, bulimia, migraine and alcoholism. It may also be of particular relevance to their unique efficacy in OCD.     

Presynaptic 5-HT1A is Related to 5-HTT Receptor Density in the Human Brain

5-Hydroxytryptamine (5-HT or serotonin) is an important neurotransmitter for a number of brain functions and widely distributed throughout the brain. Physiological and pharmacological relationship between 5-HT1A receptors and serotonin transporter (5-HTT) in the regulation of 5-HT neurotransmission has now been documented. A relationship between 5-HT1A receptors and 5-HTT is also suggested by the pathophysiology of depression and the mechanism of action of antidepressants. We have scanned 42 healthy adults with both [11C] WAY-100635 and [11C] DASB to investigate the anatomical co-distribution of multiple serotonergic markers. We hypothesized that lower 5-HTT densities in the dorsal raphe nucleus (DRN) and limbic regions will be accompanied by lower 5-HT1A receptor density in the same regions, contributing to the 5-HT1A receptor desensitization. In addition, variations in DRN 5-HT1A receptor density can theoretically influence the density and/or function of other serotonin receptor subtypes and the 5-HTT consequent to changes in serotonergic tone. In a comparatively large sample of volunteers, we have shown that the relationship between 5-HT1A and 5-HTT PET indices was complex. We were unable to demonstrate robust, intra-regional relationships between 5-HT1A and 5-HTT densities. Inter-regionally, DRN 5-HT1A receptors were related to cortical (temporal and frontal regions) and paralimbic (insula), but not limbic 5-HTT. This latter finding may reflect differences in 5-HT tone between individuals, and highlights probable substrates sensitive to variations in DRN 5-HT function.     

The effect of mepiprazole on central monoamine neurons. Evidence for increased 5-hydroxytryptamine and dopamine receptor activity

In combined biochemical, histochemical and functional studies on central monoamine neurons it has been shown that a pyrozolyl derivative with a phenyl piperazine side-chain (PAP) exerts marked effects on central dopamine (DA) and particularly 5-hydroxytryptamine (5-HT) neurons. The brain 5-HT turnover was reduced with doses down to 0.25 mg/kg, and spontaneous overflow of radioactivity from ³H-5-HT-labelled cortical slices was markedly increased by PAP in a concentration of 10^?6 M. PAP may therefore cause extragranular release of 5-HT stores, since the 5-HT levels were not affected. In agreement with this view, sexual behaviour in the female rat, which is controlled by an inhibitory 5-HT pathway, was inhibited by low doses (0.1–0.5 mg/kg) of PAP. The extensor hindlimb reflex, which is dependent of 5-HT receptor activity, was only increased with higher doses (2.5–10 mg/kg), suggesting that the spinal 5-HT nerve terminals are less sensitive to the releasing action of PAP. A certain direct activation of spinal 5-HT receptors may also be involved, since the actions of PAP in the spinal cord were independent of presynaptic 5-HT stores. The actions of PAP on the DA neurons mainly involve a presynaptic action in the DA nerve terminals leading to increased DA receptor activity. This action may primarily involve a blockade of DA uptake (50% inhibition at 10^?6 M) and/or an extragranular release of DA (two-fold increase in spontaneous overflow at 10^?6 M). The DA turnover was not clearly affected, although a trend to a reduction was observed especially in the nuc. accumbens, probably as a result of a compensatory nervous feedback reducing nervous impulse flow. In agreement with the view mentioned above, PAP mimics amphetamine and not apomorphine in the rotometer model which reveals changes in DA receptor activity. PAP in doses of 0.5–1 mg/kg causes a turning towards the denervated side. The brain noradrenaline (NA) turnover is only significantly increased with somewhat higher doses (5–10 mg/kg) and may be related ot NA receptor blockade, since the L-DOPA-induced increase in flexor activity is blocked by PAP in doses down to 0.5 mg/kg.It is suggested that the extragranular release of 5-HT caused by PAP is partly responsible for the inhibition of conditioned avoidance behaviour and the reduction of threatening behaviour found after PAP in low doses (0.05–0.5 mg/kg). In the clinic, PAP may prove to be a new therapeutic tool in the treatment of depressions due to 5-HT deficiency. Its actions on DA terminals may also prove helpful in this respect. When combined with L-DOPA, PAP may also help to alleviate the motor deficits in parkinsonian patients with a moderate degree of degeneration of the DA system in view of its action on DA uptake and/or release.