白松片对慢性应激大鼠海马单胺类神经递质含量的影响

目的:观察中药白松片对应激大鼠海马单胺类神经递质含量的影响。方法:健康成年雄性SD大鼠42只,随机分为正常对照组、模型对照组、氟西汀对照组(1.8mg·kg-1)及白松片3个剂量(4.32,13.0,21.6g·kg-1,生药量)组。每只大鼠每日灌胃给药1次,连续14d。给药d6始,通过强迫游泳建立应激大鼠模型。用高效液相色谱-电化学法测定大鼠海马单胺类神经递质及其代谢产物的含量。结果:模型对照组大鼠海马去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)含量及多巴胺/3,4-二羟苯乙酸(DA/DOPAC)和5-羟色胺/5-羟吲哚乙酸(5-HT/5-HIAA)的比值分别为(4.7±s1.3)nmol·g-1,(47±12)nmol·g-1,(0.97±0.22)nmol·g-1,19±4,0.23±0.06,低于正常对照组(P<0.05或P<0.01);NE/5-HT比值(4.9±0.9)高于正常对照组(P<0.01);用白松片预防给药可使模型大鼠海马NE,DA和5-HT含量及NE/5HT,DA/DOPAC和5-HT/5-HIAA的比值恢复至正常水平(P<0.05或P<0.01)。结论:白松片可能通过提高NE,DA及5-HT的含量并降低其代谢率来发挥其抗抑郁作用。     

脊髓NMDA受体在慢性内脏高敏大鼠中作用研究Ⅰ

目的从整体行为学角度探讨脊髓NMDA受体在慢性内脏高敏大鼠中的作用。方法选用SD大鼠,模型组大鼠在出生后d8~d15内,每天接受一次结直肠扩张刺激;对照组除了不行结直肠扩张刺激外,其他情况同模型组。大鼠成年后用腹壁撤退反射(AWR),进行肠道敏感性评估。观察两组鞘内注射MK-801前后AWR评分和腹外斜肌对结直肠扩张刺激的反应是否存在差异。结果①在20~60mm-Hg CRD时,模型组AWR评分明显高于对照组(P<0.05)。②鞘内注射不同浓度MK-801后,模型组AWR测痛阈呈剂量依赖性升高(P<0.05),而对照组没有表现出明显的剂量依赖性。③鞘内注射MK-801(1.5mol·L-1)后,模型组腹外斜肌对CRD反应较给药前明显降低(P<0.05),肌电测痛阈明显升高(P<0.05);而对照组给药前后无改变。④模型组结直肠病理检查未见明显病理性改变。结论大鼠脊髓NMDA受体可能参与慢性肠道高敏感机制。     

美洛昔康改善慢性应激大鼠抑郁行为的机制初探

目的初步探讨美洛昔康对慢性应激大鼠抑郁行为的影响及其机制。方法采用42 d慢性温和不可预知的刺激方法建立大鼠抑郁模型,美洛昔康(1、3 mg·kg~(-1))和舍曲林(5 mg·kg~(-1))在造模开始21d后灌胃给药,每天1次,连续21d。旷场实验和强迫游泳实验检测大鼠行为学变化,酶联免疫吸附法检测大鼠皮层PGE_2、TNF-α含量变化,高效液相色谱法(HPLC)分析大鼠皮层NE、DA、DOPAC、5-HIAA的含量变化,免疫组化法检测皮层5-HI1AR的表达变化。结果与正常组比较,慢性应激大鼠在旷场实验中水平和垂直运动减少(P<0.01),强迫游泳实验中静止不动时间延长(P<0.01),皮层中PGE_2、TNF-α含量增加(P<0.01),NE、DA、DOPAC、5-HIAA的含量明显减少(P<0.01),同时5-HT1AR(P<0.05)的表达减少。与模型组相比,美洛昔康能明显改善CUMS大鼠的抑郁行为,降低大鼠皮层PGE_2与TNF-α含量(P<0.01)的同时增加NE、DA、DOPAC和5-HIAA含量(P<0.05或P<0.01),上调5-HT1AR的表达(P<0.01)。结论美洛昔康能明显改善CUMS诱导的大鼠抑郁行为,其机制可能与其改善皮层炎症反应损伤,重建单胺递质系统平衡有关。     

山奈酚对乳腺癌抑郁模型大鼠的抗抑郁作用研究

目的 探讨山奈酚对实验性乳腺癌抑郁大鼠的抗抑郁作用。方法 90只大鼠随机分为对照组、乳腺癌组、抑郁组、复合模型组、氟西汀组、山奈酚组,每组15只。通过慢性不可预知性轻度应激方法建立大鼠抑郁模型,以二甲基苯蒽为诱导剂建立乳腺癌大鼠模型。采用旷场实验垂直运动次数及水平活动总路程观察各组大鼠自主活动;液质联检分析各组大鼠脑内海马及前额叶皮质单胺类神经递质,包括去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)和5-羟色胺(5-hydroxytryptamine,5-HT)含量的变化。结果 乳腺癌组自主活动均减少,但与对照组比较无显著性差异;抑郁组和复合模型组自主活动减少,与对照组比较差异均有显著性(P<0.01);与复合模型组相比,山奈酚组与氟西汀组垂直运动次数及水平活动总路程均显著增加(P<0.05或P<0.01)。与复合模型组比较,氟西汀组海马区DA、5-HT含量显著增高(P<0.01),前额叶皮质DA、NE、5-HT浓度均显著性增高(P<0.05);山奈酚组与复合模型组比较,海马部位NE含量明显增高(P<0.05),前额叶皮质部位DA、NE、5-HT浓度均显著性增高(P <0.05或P <0.01)。结论 山奈酚具有显著抗大鼠抑郁作用,可能通过提高前额叶皮质部位NE、DA、5-HT递质水平达到抗抑郁作用。     

立体定向毁损内囊前肢对大鼠脑内递质的影响

目的探讨内囊前肢毁损后AMP模型大鼠脑内单胺类递质含量的变化,为难治性精神病病因的研究和外科治疗提供参考.方法经腹腔注射苯丙胺(AMP)制作精神病动物模型,应用立体定向技术电极毁损大鼠内囊前肢,采用荧光分光光度法和放射免疫法测定大鼠前额叶、间脑和脑干多巴胺(DA)、5-羟色胺(5-HT)和去甲肾上腺素(NE)的含量.结果内囊前肢毁损组前额叶DA和NE低于假毁损组(P＜0.01),5-HT均高于假毁损组(P＜0.01);毁损组间脑DA、NE均低于假毁损组(P＜0.01),5-HT高于假毁损组(P＜0.01);脑干 DA低于假毁损组(P＜0.01),5-HT高于假毁损组(P＜0.01).结论 AMP模型大鼠前额叶DA含量增高、5-HT和NE含量下降,间脑DA、NE含量增高、5-HT含量下降,脑干DA含量增高,5-HT含量下降.立体定向毁损内囊前肢改变了脑内单胺类递质的水平.     

奥氮平致大鼠体重增加的中枢5-羟色胺作用机制

目的探讨奥氮平致大鼠体重增加的中枢5-羟色胺(5-HT)作用机制。方法 20只SD雄性大鼠随机均分为模型组(奥氮平1.2mg·kg-1·d-1灌胃)和对照组(等量生理盐水灌胃)。两组给药前和给药2、4、8周测量体重和摄食量;给药8周,采用旷场试验测试大鼠自主活动,高效液相色谱-电化学检测法测定大鼠中缝背核5-HT和5-羟吲哚乙酸(5-HIAA)含量。结果给药8周后,模型组大鼠摄食量多于对照组[(32.56±2.13)g/d vs.(24.25±2.60)g/d](P<0.01),体重大于对照组[(309.56±13.74)g vs.(269.50±10.90)g](P<0.01),水平运动距离[(448.22±74.63)cm vs.(1260.00±115.81)cm]和垂直竖立次数[(6.89±2.93)次vs.(17.13±4.82)次]少于对照组(P<0.01)。给药8周后,模型组大鼠5-HT含量高于对照组[(50.11±15.02)ng/g vs.(14.63±4.00)ng/g](P<0.01),5-HIAA含量[(183.44±27.91)ng/g...     

川菊止痛胶囊对偏头痛模型大鼠的改善作用及机制研究

目的:研究川菊止痛胶囊对偏头痛模型大鼠的改善作用及机制。方法:将SD大鼠随机分为正常组、模型组、化学药阳性对照组(佐米曲普坦片,0.004 05 g/kg)、中药阳性对照组(复方羊角颗粒,4.32 g/kg)和川菊止痛胶囊高、中、低剂量组(1.6、0.8、0.4g/kg),每组10只。每天灌胃给药1次,连续给药5 d。末次给药30 min后,除正常组外,其余各组大鼠头颈部皮下注射硝酸甘油(10 mg/kg)复制偏头痛模型。以挠头次数为指标评价造模后2 h内(30 min为一个时间段)各组大鼠行为学变化;造模4 h后,采用全自动血液流变仪检测各组大鼠全血黏度(低切、中切、高切)、血浆黏度及红细胞聚集指数、红细胞刚性指数等血液流变学参数;酶联免疫吸附试验(ELISA)检测各组大鼠血清中一氧化氮(NO)、一氧化氮合成酶(NOS)、内皮素1(ET-1)、降钙素(CGRP)和脑组织中5-羟色胺(5-HT)、5-羟基吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)水平。结果:与正常组比较,模型组大鼠在各时间段挠头次数显著增加(P<0.01);血清中NO、NOS和CGRP水平显著升高(P<0.01),ET-1水平显著降低(P<0.01);脑组织中5-HT、DA和NE水平显著降低(P<0.01),5-HIAA水平显著升高(P<0.01);全血黏度(低切)、红细胞聚集指数、红细胞刚性指数均显著升高(P<0.05),血浆黏度显著降低(P<0.01)。与模型组比较,化学药阳性对照组(0～120 min)、中药阳性对照组(60～90min)和川菊止痛胶囊高(30～120 min)、中(60～90 min)剂量组大鼠挠头次数显著降低(P<0.05或P<0.01);中药阳性对照组和川菊止痛胶囊高、中剂量组大鼠全血黏度(低切)和红细胞聚集指数显著降低(P<0.05或P<0.01);化学药阳性对照组和川菊止痛胶囊高、中剂量组大鼠血清中NO、NOS、CGRP水平显著降低(P<0.05或P<0.01),ET-1水平显著升高(P<0.01),脑组织5-HT、DA、NE水平显著升高(P<0.05或P<0.01),5-HIAA水平显著降低(P<0.05)。结论:川菊止痛胶囊对偏头痛模型大鼠的改善作用与降低血清中NO、NOS、CGRP水平及升高脑组织中5-HT、DA、NE水平有关。     

刺五加苷E对小鼠学习及记忆能力的影响

目的探讨刺五加苷E对对氯苯丙氨酸(PCPA)造模小鼠学习记忆行为以及对海马内单胺类神经递质5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NA)的影响。方法 Balb/c小鼠随机分为空白组,模型组,阳性药组,刺五加苷E(ELE)高、中、低剂量组。以PCPA腹腔注射建立小鼠损伤模型,给药14d后Morris水迷宫实验测试小鼠的学习记忆能力,Elisa试剂盒测定小鼠海马组织中5-HT、5-HIAA、DA、NA的含量。结果行为学结果显示,模型组小鼠穿越平台次数较空白组明显降低(P<0.01),ELE高、中剂量组可明显增加小鼠穿越平台次数(P<0.01),模型组小鼠5-HT、5-HIAA较空白组显著降低(P<0.01),NA也显著降低(P<0.05)。ELE各剂量组5-HT、5-HIAA含量较模型组显著升高(P<0.01或P<0.05),ELE高、中剂量可明显改善DA、NA的含量,且与模型组相比,差异显著(P<0.01或P<0.05)。结论ELE提高PCPA造模小鼠学习记忆能力可能与其改善海马组织中5-HT、5-HIAA、DA和NA的含量有关。     

半夏泻心汤对偏头痛大鼠神经递质及早快基因表达的影响

目的 研究半夏泻心汤(BXXXT)对实验性偏头痛模型大鼠神经递质及早快基因表达的影响.方法 将60只SD健康大鼠随机分为正常组、模型组、阳性组、BXXXT高、中、低剂量组.ig生理盐水予正常组、模型组大鼠,其余各组大鼠ig BXXXT,连续7d,末次给药后1h皮下注射硝酸甘油10 mg·kg-1造模.用ELISA法测定大鼠血清中5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)的含量;HE染色观察大鼠脑干组织细胞形态学的变化;免疫组化染色测定大鼠脑干中c-jun基因的表达.结果 与模型组比较,BXXXT可升高大鼠血浆中DA、NE、5-HT的水平,降低5-HIAA水平和大鼠脑干中c-jun基因的表达.结论 BXXXT对实验性偏头痛大鼠具治疗作用.     

舒通安胶囊对海洛因依赖者血单胺类递质的影响

目的:了解5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)在海洛因依赖发病中的意义,观察舒通安胶囊对海洛因依赖者单胺类递质的影响。方法:用荧光分光光度法检测56例海洛因依赖者(注射组35例、烫吸组21例)治疗前后和23例正常人血浆及血小板5-HT、5-HIAA、DA和NE含量。结果:海洛因依赖者血浆5-HT、5-HIAA、DA和NE含量均高于对照组(P<0.01),烫吸组血浆DA、5-HIAA含量低于注射组(P<0.05,P<0.01),经舒通安胶囊治疗后血浆5-HT、5-HIAA、DA和NE含量显著降低(P<0.01),其中烫吸组NE高于注射组(P<0.05)。海洛因依赖者血小板5-HT、5-HIAA、DA和NE含量均高于对照组(P<0.01),烫吸组血小板5-HT、DA含量低于注射组(P<0.01),经舒通安胶囊治疗后血小板5-HT、5-HIAA、DA和NE含量显著降低(P<0.01),其中烫吸组DA、5-HT、NE高于注射组(P<0.01,P<0.05)。结论:单胺类递质在海洛因依赖的病理过程可能有重要意义,舒通安胶囊可调节海洛因依赖者外周单胺类递质水平。     

Correlative changes of serotonin and catecholamines with pharmacokinetic alterations of imipramine in rat brain

Rats were given i.p. imipramine (20 mg/kg), acutely or chronically, and the levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites in the brain at different times were compared with the concentrations of imipramine and desipramine. The levels of 5-HT, DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain did not appear to be affected by quantitative alterations in the concentrations of imipramine and desipramine. The level of 5-hydroxyindole acetic acid (5-HIAA) was reduced and the level of 3-methoxy-4-hydroxyphenylglycol (MHPG) tended to decrease 3 h after imipramine administration in acutely treated rats. The reduced level of 5-HIAA was maintained during the chronic treatment with imipramine, whereas the MHPG level increased and the NE level decreased. The decrease in 5-HIAA depended on the concentration of imipramine in the brain, whereas the changes in the levels of NE and MHPG appeared to be caused by desipramine. The present studies show that pharmacokinetic variations of imipramine in the brain might correlate with the altered levels of 5-HIAA, NE and MHPG.     

脑缺血再灌注小鼠脑内不同神经核团单胺递质及其代谢产物的变化

目的　测定脑缺血再灌注后小鼠脑内不同神经核团单胺递质及其代谢产物的动态变化。方法　阻断小鼠双侧颈总动脉 (CCAO)进行缺血再灌 ,于术后当天 (d 0 )及d 1、3、5、2 0用HPLC ECD动态检测小鼠海马 ,纹状体 ,皮层的神经递质及其代谢产物的变化。结果　与假手术对照组相比 ,脑缺血再灌注小鼠术后上述神经核团去甲肾上腺素 (NE) ,多巴胺 (DA) ,5 羟色胺 (5 HT)等神经递质及其代谢产物含量降低 ,其中海马表现尤为明显。结论　脑内多个神经系统参与了脑缺血再灌注小鼠的病理过程 ,小鼠海马对缺血损伤最为敏感。提示脑缺血再灌注后海马神经递质异常是其后期行为表现的物质基础 ,是临床治疗中应予以重视的靶点     

左金丸总生物碱对束缚水浸应激性胃溃疡模型大鼠神经体液调节的影响

目的左金丸是黄连和吴茱萸按6∶1配伍组成,临床常用于胃溃疡的治疗。该文主要探讨左金丸总生物碱(ZJP-TA)对束缚水浸应激性胃溃疡模型大鼠神经体液调节的影响。方法采用束缚水浸法复制大鼠胃溃疡模型,测定ZJP-TA对大鼠胃溃疡指数,胃黏膜TNF-α含量的影响。测定大鼠海马、皮质、下丘脑、纹状体等脑区中单胺类神经递质5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)及其代谢产物5-羟吲哚乙酸(5-HIAA)含量以及肾上腺组织中NE和肾上腺素(E)含量的影响。结果预先口服ZJPTA可明显降低应激性胃溃疡大鼠的溃疡指数,明显降低胃黏膜中TNF-α的含量。各剂量ZJPTA可不同程度降低大鼠脑组织单胺类神经递质的浓度,与模型组比较差异具有显著性(P<0.05或P<0.01)。模型组肾上腺组织NE和E含量明显升高,ZJPTA能明显抑制其升高(P<0.05或P<0.01)。结论 ZJPTA可通过神经体液调节作用,对抗应激性胃溃疡损伤。     

Changes of serotonin and catecholamines are related to pharmacokinetic alterations of clomipramine in rat brain.

When rats received a single i.p. injection of clomipramine (20 mg/kg), clomipramine and desmethylclomipramine were rapidly distributed into the brain and their concentrations were markedly higher in the brain than in the serum, while the concentration of the metabolite in the brain was much lower than that of clomipramine. Chronic administration of clomipramine gradually increased the concentrations of the metabolite in both serum and brain, but did not significantly change those of clomipramine. The levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites in the brain were compared with the concentrations of clomipramine and desmethylclomipramine at different times. The levels of 5-HT, NE, DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain did not appear to be affected by changes in the concentrations of the drug and metabolite. The level of 5-hydroxyindole acetic acid (5-HIAA) was reduced following clomipramine injection and the reduced level was maintained during chronic treatment. Chronic treatment for more than 7 days increased the 3-methoxy-4-hydroxyphenylglycol (MHPG) level with no alteration of NE level. This elevation appeared to be induced by desmethylclomipramine.     

高同型半胱氨酸血症对慢性应激模型大鼠行为学及神经生化的影响

目的研究高同型半胱氨酸血症(Hhcy)对慢性不可预见应激模型大鼠行为学、神经递质及神经营养因子水平的影响。方法以高蛋氨酸饮食喂养大鼠制作Hhcy模型(Hhcy组,12只);另选24只大鼠,均分为普食组和对照组,均给予普通饮食喂养;Hhcy组与普食组给予慢性不可预见性刺激。比较三组的学习记忆能力、海马组织5-羟色胺(5-HT)和5-羟基吲哚乙酸(5-HIAA)含量以及脑脊液中神经营养因子(BDNF)水平。结果水迷宫实验中,Hhcy组目的象限停留时间比普食组短(P<0.05);Hhcy组海马5-HIAA含量和脑脊液中BDNF含量均较普食组低(P<0.05)。结论Hhcy可致慢性应激模型大鼠学习记忆能力的下降,加重神经递质及生长因子水平的异常,可能为抑郁症的危险因素之一。     

Alterations of central norepinephrine, dopamine and serotonin in several strains of mice following acute stressor exposure

Exposure to inescapable footshock provoked region-specific alterations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) activity across six strains of mice (A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J and CD-1). The stressor provoked reductions of hypothalamic NE and increased MHPG accumulation in all strains. In contrast, the effects of the stressor on NE activity in the hippocampus and locus coeruleus varied appreciably across strains. In the mesocortex and nucleus accumbens shock induced an increase of DOPAC accumulation and pronounced reductions of DA in some strains, while in others these variations were less pronounced or entirely absent. Stressor-provoked alterations of 5-HT and 5-HIAA were most evident in the mesocortex. Strain-specific neurochemical alterations following footshock are discussed relative to stressor-induced behavioral disturbances and animal models of depression.     

麻醉剂量羟甲芬太尼对大鼠脑内单胺递质及其代谢物含量的影响

Effects of ohmefentanyl in anesthetic dose on the levels of monoamine transmitters and their metabolites in rat brain were studied using the HPLC coupled with electrochemical detection in this paper. The results showed that OMF in anesthetic dose 4.0 μg·kg^-1 increased the contents of 5-HT in striatum from 0.05±0.02 to 0.19±0.08 μg·g^-1 wet tissue (P<0.01) and 5-HIAA levels in striatum, hippocampus and frontal cortex from 0.06±0.04,
0.05±0.05, and 0.05±0.04 to 0.28±0.08, 0.13±0.07, and 0.11±0.07 μg·g^-1 wet tissue (P<0.01 or P<0.05) respectively. The levels of DOPAC in striatum, frontal contex and brain stem were decreased from 1.47±0.69, 0.19±0.15, and 0.07±0.05 to 0.92±0.23, 0.08±0.05, and 0.04±0.02 μg·g^-1 wet tissue (P<0.05) respectively. The HVA levels in hippocampus and hypothalamus were raised from 0.01±0.00, 0.03±0.02 to 0.04±0.03, 0.07±0.05 μg·g^-1 wet tissue (P<0.05), respectively. There were no obvious changes in DA, NE and MHPG levels. The raise of 5-HT contents may be related to the anesthetic activity of OMF.     

Early intervention with fluoxetine reverses abnormalities in the serotonergic system and behavior of rats exposed prenatally to dexamethasone

Many psychiatric disorders emerge after adolescence. Among a variety of predisposing factors, prenatal stress has been thought to cause the symptoms of anxiety disorders. We recently reported that prenatal dexamethasone (DEX) exposure, which mimics some aspects of prenatal stress, induced anxiety-related behaviors in male offspring when they reached adulthood. Before the emergence of behavioral changes, abnormalities occurred in the hypothalamic-pituitary-adrenal axis during postnatal development. In the present study, we found abnormalities in serotonin (5-HT) signaling, including decreased expression of 5-HT(1A) receptor (5-HT(1A)-R) mRNA in the medial prefrontal cortex (mPFC) and 5-HT content in the hippocampus at postnatal week (PW) 4. These results support using early therapeutic interventions with serotonergic drugs to prevent late-emerging anxiety symptoms. To test this hypothesis, we treated rat pups born to DEX-administered mothers with fluoxetine (FLX), a selective serotonin reuptake inhibitor commonly used as an anti-anxiety medication, via breast milk from postnatal day (PD) 2-21. Anxiety-related behaviors examined at PW11-13 were not observed in the prenatally DEX-exposed offspring that were treated with FLX. Likewise, FLX increased 5-HT concentrations in the mPFC and ventral hippocampus at PW3 and normalized 5-HT(1A)-R mRNA concentrations in the mPFC at PW4. The decrease in brain-derived neurotrophic factor (BDNF) protein in the mPFC and dorsal hippocampus was also restored at PW4. Furthermore, administration of the 5-HT(1A)-R full agonist (R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin from PD2 to 21 also prevented the emergence of behavioral abnormalities in the prenatally DEX-exposed offspring, implicating the involvement of 5-HT(1A)-Rs in the neonatal FLX effect. Collectively, an early pharmacological intervention to normalize serotonergic transmission effectively suppressed the emergence of symptoms induced by prenatal DEX exposure in rats.