日本血吸虫体内5-HT和GABA的神经生物学研究

5-羟色胺(5-HT)、γ-氨基丁酸(GABA)为日本血吸虫体内重要的生物活性物质。本文简要介绍:1药物对日本血吸虫体长和运动性的影响;2日本血吸虫体内5-HT的含量;3日本血吸虫体内5-HT的合成及降解;4抗血吸虫药物对虫体内5-HT含量的影响;5日本血吸虫体内5-HT受体特性;6药物对日本血吸虫体内环核甘酸(cAMP)的影响;7GABA含量、来源;收稿日期:2002-05-03基金项目:国家自然科学基金资助项目(39170578)作者简介:余祖功(1966-),男,河南省商城人,南京农业大学动物医学院讲师,在职博士生,主要从事神经生物学的研究和新兽药及新制剂的研究工作。8日本血吸虫GABA受体特性。     

水牛实验血吸虫病的药物治疗效果比较

就目前我国家畜血吸虫病的3种药物进行人工感染水牛血吸虫病的不同途径治疗比较试验，并测定吡喹酮的有效血药浓度。结果以吡喹酮30mg／kg和15-25mg／kg,硝硫氰胺2mg／kS及硝硫氰醚15mg／kg应用口服、肌注或第三胃注射等不同疗法的灭虫效果和灭雌效果显著。建议在我国疫区根据各地习惯、经济和技术条件择药应用。并对牛体内残存雄虫情况进行了讨论。     

硝硫氰醚防治猪膜壳绦虫病效果好

硝硫氰醚防治猪膜壳绦虫病效果好除吡喹酮对猪膜壳绦虫病有确切疗效和硫双二氯酚有一定效果外，未有其他有效药物。硝硫氰醚是一个广谱、高效、低毒的国产驱虫新药。作者首次用于治疗猪膜壳绦虫病。共治疗患猪１１头，均获良效。治法：猪经２４小时饥饿后，于次日清晨，将...     

吡喹酮与硝硫氰胺治疗绵羊日本血吸虫病的疗效观察

吡喹酮(Praziguontol,Dioncit,FMBA—8440)是我国继硝硫氰胺后合成的又一广谱抗血吸虫药物,国内外对吡喹酮的药理作用及杀虫机制进行了一系列的研究,Webbe与James等分别报导了感染日本血吸虫田鼠和猴的实验治疗结果。国内范必勤等首次报导了人工感染     

IgG1型单克隆抗体和吡喹酮协同预防日本血吸虫病的研究

6组昆明系小鼠人工感染日本血吸虫尾蚴前2小时,组1和组2胃饲低剂量吡喹酮(20mg/kg),并分别腹腔注入鼠抗日本血吸虫IgG_1型单克隆抗体ISj51和ISj55作被动免疫,4天后重复1次,4周后剖杀集虫。结果表明,单抗合并吡喹酮的组1和组2的减雌率分别为45.32％和42.95％,均明显高于(p<0.01)仅作腹腔被动免疫转移ISj 51和ISj 55单抗的组3和组4(分别为15.11％和19.44％),亦高于(p>0.05)仅用单剂吡喹酮的组5(37.41％)。2株单抗在巨噬细胞和嗜酸性粒细胞的介导下,杀伤童虫率接近1:2稀释的8周阳性鼠血清(分别为37.50％,46.88％和48.00％,41.18％)。提示:鼠抗日本血吸虫IgG_1型单抗协同低剂量吡喹酮,具有预防日本血吸虫感染,提高灭雌率,降低吡喹酮毒副作用的优点,对控制和预防日本血吸虫病的传播具有一定的意义。     

复方吡喹酮、吡喹酮及丙硫咪唑治疗猪囊虫病的对比试验

应用复方吡喹酮、吡喹酮及丙硫咪唑治疗人工感染囊虫病猪33头,于治疗后4h、24h、77d及100d扑杀,对病猪肌肉组织、脑组织及囊虫进行了病理组织学和超微结构观察。结果表明,三种药物对病猪体内囊虫均具有杀死作用。治疗后24h,复方吡喹酮组病猪体内囊虫全部死亡,而吡喹酮组及丙硫咪唑组病猪体内仍有囊虫存活,治疗后77d及1O0d,复方吡喹酮组病猪体内囊虫全部死亡并被吸收;吡喹酮组病猪体内有多量失去生物活力的囊虫残留;内硫咪唑组病猪体内仍有多量囊虫存活。本实验证实,复方吡喹酮治疗猪囊虫病比吡喹酮及丙硫咪唑的治疗效果迅速而彻底.     

放射配体受体分析法对日本血吸虫体内 5-HT受体的测定

采用放射配体-受体分析法(RLBA)测定了日本血吸虫体内5-羟色胺(5-HT)受体及螺环哌啶酮(spiroperidol)对5-HT受体与3H-5-HT结合反应的影响。结果证实:日本血吸虫体内存在5-HT受体,与配体5-HT可进行饱和的、特异的结合,其Scatchard图呈下凹曲线,表明5-HT受体的复杂性和不均一性。其最大结合容量(Bmax)为210.4fmol/mgprotein,解离常数(Kd)为0.585pmol/L,螺环哌啶酮对3H-5-HT与受体的结合无影响,计算Bmax为270.3fmol/mgprotein,Kd为0.327pmol/L,与前值比较,差异不显著(P>0.05)。     

20%吡喹酮注射剂在水牛体内的药代动力学研究

4头成年健康水牛采用随机交叉实验设计,分别进行吡喹酮注射剂肌注和吡喹酮片内服给药的药动学试验.吡喹酮注射剂按10 mg/kg的剂量单次肌注,吡喹酮片按20 mg/kg的剂量单次内服给药.采用高效液相色谱法测定血浆中吡喹酮的质量浓度,方法最低检测限和定量限分别为0.01 mg/L和0.062 5 mg/L.吡喹酮注射剂单剂量肌注给药,血药浓度-时间数据符合一级吸收一室开放模型,其主要动力学参数分别为:t1/2(ka)(0.45±0.029)h,t1/2(ke)(5.04±0.1 0)h,T(peak)(1.72±0.029)h,C(max)(0.87±0.006)mg/L,V(c)(8.58±0.010)L/kg,AUC(7.99±0.005)mg·L-1·h-1.吡喹酮片单剂量口服给药血药浓度-时间数据符合有吸收-室开放模型,其主要动力学参数分别为:Lagtime(0.13±0.010)h,t1/2(ka)(0.76±0.11)h,t1/2(ke),(1.31±0.076)h,T(peak)(3.84±0.026)h,C(max)(0.51±0.006)mg/L,V(c)(26.07±1.221)L/kg,AUC(7.99±0.005)mg·L-11·h-1.肌注相对生物利用度为(232±12.9)%.研究结果表明,20%吡喹酮注射剂肌注给药吸收迅速且完全,具有较高的生物利用度;吡喹酮吸收后在体内广泛分布.     

三种药物对猪棘头虫LDH同工酶的抑制试验

根据猪棘头虫与宿主（猪）血清的ＬＤＨ同工酶的差异，用０．１％硝硫氰醚、０．１％丙硫咪唑和０．１％吡喹酮分别对猪棘头虫雄虫、雌虫和猪血清的ＬＤＨ同工酶进行了抑制试验，结果除硝硫氰醚对蛭形巨吻棘头虫雄虫、雌虫的ＬＤＨ同工酶有抑制作用外，其余的试验组与对照组均无差异。硝硫氰醚对雄虫ＬＤＨ同工酶的第２、３、４带和雌虫ＬＤＨ同工酶的第２、３带有不同程度的抑制作用，特别是雌虫ＬＤＨ同工酶的第２带最敏感，在０．１％的浓度下，该酶带被完全抑制，即没显示出来，硝硫氰醚对雄虫和雌虫ＬＤＨ同工酶的极弱带（它们各自的第１带）均无抑制作用；临床实验也显示出硝硫氰醚对治疗猪棘头虫病有一定疗效，这些表明硝硫氰醚抑制蛭形巨吻棘头虫的ＬＤＨ同工酶活力可能是该药物对该虫体的作用机理之一。     

抗日本血吸虫药物的研究进展

日本血吸虫是一种重要的人兽共患寄生虫,具有重要的公共卫生和社会经济意义,引起国内外学者的高度关注。作者综述了抗日本血吸虫药物的最新进展,重点综述了吡喹酮、青蒿素和硝硫氰胺的药物代谢、作用机制和临床应用,为日本血吸虫病的防治奠定理论基础。     

不同猪种5-羟色胺受体基因的表达及其与肉质的相关性分析

为研究5-羟色胺（5-HT）受体基因在不同猪种的表达及其与肉质的关系,试验选取淳安花猪与杜长大三元猪各12头,同时饲喂,达上市体重时分别屠宰,测定胴体、肉质性状及肌肉、脂肪中的5-HT受体基因表达量。结果表明：淳安花猪、杜长大三元猪的平均屠宰体重分别为88.1、102.4kg;淳安花猪的板油率、背膘厚、肌内脂肪等指标均显著高于杜长大三元猪（P〈0.05）;屠宰率、眼肌面积杜长大三元猪显著高于淳安花猪（P〈0.05）。5-HT2A、5-HT7受体基因在2个猪种脂肪组织中的表达量均显著高于肌肉组织（P〈0.05）,杜长大三元猪的肌肉中5-HT2A、5-HT7表达量显著低于淳安花猪（P〈0.05）,而脂肪中表达量两猪种间差异不显著。5-HT2A、5-HT7受体基因表达量与屠宰肉质指标之间基本呈负相关,尤其是肌肉中的5-HT2A表达量,呈较强负相关（杜长大三元猪）或显著负相关（淳安花猪）。研究初步认为,5-HT受体基因在中外猪种之间存在表达差异,并与屠宰肉质性状具有相关性。     

东方田鼠肺脏裂解物筛选日本血吸虫成虫噬菌体展示cDNA文库

目的寻找与东方田鼠抗性相关的血吸虫靶基因。方法以东方田鼠肺脏裂解物为探针,亲和淘洗筛选日本血吸虫成虫（44d）噬菌体展示cDNA文库。三轮筛选后．随机挑取76个阳性噬菌体克隆进行序列测定及生物信息学分析。结果共获得了13个有效EST序列,其中8条EST序列与已知基因或表达序列标签同源,5个EST序列与已知基因或表达序列标签均无同源性,为新的表达序列标签。功能预测结果显示．这13个有效EST编码蛋白主要与血吸虫基因表达调控及蛋白质加工修饰相关。结论东方田鼠直接或间接地影响血吸虫基因表达,进而影响血吸虫的发育,可能是东方田鼠具有抗血吸虫特性的一个重要分子机理。     

Interbreed variation in serum serotonin (5-hydroxytryptamine) concentration in healthy dogs

Introduction

Serotonin (5-hydroxytryptamine [5-HT]) has several biological functions. In different species, excessive 5-HT has been linked to valvular lesions, similar to those seen in dogs with myxomatous mitral valve disease. Previous studies suggest higher 5-HT in healthy Cavalier King Charles Spaniels (CKCSs), a breed highly affected by myxomatous mitral valve disease, compared to other breeds.

高效液相色谱法测定猪血浆、全血和血小板中五羟色胺水平及其相关性分析

本试验采集43头苏淮猪的血液样本,探究利用高效液相色谱法(HPLC)测定血浆和全血五羟色胺(5-HT)的色谱条件,测定了血浆、全血和血小板中5-HT的水平,并对它们进行了相关性分析。结果:猪血浆中5-HT浓度为(45.35±2.23)μg/mL,血小板中5-HT含量为(131.31±7.86)pg/10^9,全血中5-HT浓度为(296.87±12.81)μg/mL;相关性分析显示,血小板5-HT浓度与全血5-HT浓度存在极显著正相关性(r=0.849,P<0.01),血小板5-HT浓度与血小板数量存在极显著负相关性(r=-0.549,P<0.01),但血浆5-HT浓度与全血5-HT浓度、血小板5-HT浓度无显著相关性(P>0.05)。综上,高效液相色谱法可用于测定猪血浆、全血、血小板中5-HT的水平,血小板5-HT含量与全血5-HT浓度和血小板数量之间均存在极显著相关性。     

阿魏倍半萜类对日本血吸虫作用研究

观察小鼠体内不同发育阶段日本血吸虫童虫与成虫对阿魏倍半萜类的敏感性。用定量日本血吸虫尾蚴感染小鼠,感染2 h,1、3、7、12、14、16、25、35、42 d后分别一次性灌服阿魏倍半萜类500 mg/kg。给药后4周剖检小鼠,采用门静脉灌注法收集虫体,计算减虫率。结果显示,阿魏倍半萜类对1、3、7、12、14、16、25、35、42 d龄童虫或成虫的减虫率分别为16.9%、18.0%、71.3%、50.2%、36.9%、31.3%、45.3%、58.0%、26.4%,其中以7-35 d龄虫对该药最敏感。该结果提示,阿魏倍半萜类对小鼠体内不同发育阶段日本血吸虫均有杀灭作用,对7-35 d龄虫体杀灭效果更为明显。     

5-羟色氨调控动物采食的研究进展

关于5-羟色氨(5-HT)对采食量的影响已有几十年的研究历史。机体内的5-HT主要是以必需氨基酸色氨酸(Trp)作为前体物,在大脑和肠道中合成,并在机体中发挥重要的作用。5-HT无法直接透过血-脑屏障,因此中枢神经系统和外周5-HT作为两个相对独立的系统各自发挥作用。目前,已有大量的研究表明中枢5-HT的多种受体以不同的方式调控动物采食,主要有5-HT1A、5-HT1B、5-HT2A、5-HT2C、5-HT3A、5-HT4、5-HT5A、5-HT6和5-HT7。例如,现在临床上被批准使用的抗肥胖药物氯卡色林就是一种5-HT2C受体激动剂。此外,中枢5-HT还可以协同胰高血糖素样肽-1、饥饿素和胆囊收缩素等外周激素共同调控动物采食行为。外周5-HT也能够通过介导胰高血糖素样肽-1和胆囊收缩素来诱导饱腹感。畜禽生产中主要通过在饲料中添加Trp来增加动物体内5-HT的合成。但目前对于Trp对畜禽采食量的调控机制的研究尚不完善,且有研究表明,不同浓度的Trp对动物采食量的影响不同,不同畜禽饲料中最适Trp的浓度也不同。而Trp主要是通过其代谢产物5-HT来调控动物采食。作者查阅了大量国内外最新的研究成果,从中枢和外周两个途径对5-HT调控动物采食行为的研究进展作一综述,期望通过对Trp的代谢产物5-HT对动物采食调控机制的探讨,为Trp在畜禽生产中的应用提供一定的理论依据。     

The Influence of Training and Simulated Race on Horse Plasma Serotonin Levels

Exercise represents a physical stress that challenges homeostasis affecting central and peripheral serotoninergic systems. The influence of the exercise on circulating serotonin (5-hydroxytryptamine [5-HT]) levels depends on training state as well as the exercise protocol. The purpose of the present research was to determine changes of plasma 5-HT in sport horses in response to training (T) and simulated race (SR) and in addition to assess the possible presence of significant differences on circulating 5-HT between two different sessions of exercise. In particular, the research was carried out on 18 trained horses performing daily training and race activity. Plasma 5-HT levels were analyzed in platelet poor plasma fraction by ELISA assay at T0 (before exercise), T1 (30 minutes after exercise) and T2 (2 hours after exercise). The hypothesis was that both exercise sessions could affect plasma 5-HT levels. Results showed a significant increase of plasma 5-HT levels at T1, compared with T0, both after simulated race and training activity. These effects are probably related to an increased 5-HT release from platelets and/or an increased peripheral 5-HT synthesis induced from exercise. At T2, plasma 5-HT concentrations showed a significant decrease to physiological levels in both sessions. Moreover, plasma 5-HT levels at T1 (SR) were significantly higher than those at T1 (T). Targeting peripheral 5-HT could be useful to assess the physiological adaptability of horses to the exercise, together with other selection techniques of sport horses.     

千里光超微粉的镇痛机制研究

为研究中草药千里光（Senecio scandens Buch.-Ham）超微粉的镇痛机制，为千里光镇痛剂的开发利用提供参考依据，本研究以6周龄昆明小鼠为试验动物，制备千里光超微粉混悬液，设千里光超微粉高（360 mg/kg体重）、中（180 mg/kg体重）、低（90 mg/kg体重）剂量组，以灌胃方式连续给药7 d后进行后续相关试验，通过甲醛致痛模型和热浴甩尾法验证其镇痛作用并用以区分中枢镇痛和外周镇痛作用，通过纳洛酮颉颃试验、利血平颉颃试验及对小鼠血清和脑组织中五羟色胺（5-HT）和一氧化氮（NO）浓度的检测等方法来探究其中枢镇痛和外周镇痛机制。结果显示，千里光超微粉能提高甲醛致痛模型和热浴甩尾法中小鼠的痛阈值，且呈剂量-效应关系；纳洛酮和利血平分别作为阿片受体阻断剂和抗去甲肾上腺素能神经末梢药，可部分颉颃千里光超微粉的镇痛作用；千里光超微粉可显著提高脑组织5-HT的浓度，降低血清中5-HT的浓度（P<0.05），但对于脑组织和血清中NO的浓度调节效果不明显。结果表明，千里光超微粉具有中枢性和外周性镇痛作用，其镇痛途径与阿片受体存在一定关系，可通过抑制囊泡膜对递质去甲肾上腺素（NE）的主动摄取过程而间接发挥镇痛作用；还可通过升高中枢NO和5-HT的浓度及降低外周NO和5-HT的浓度来发挥其镇痛作用，但对于NO的浓度调节效果不明显。     

Reproduction strategy of nocturnal marine molluscs: running for love

The cost of reproduction is the core driver of life history evolution in animals. This paper demonstrates that the cumulative distance moved and the duration of movement of sexually immature abalones, Haliotis discus hannai, kept in various male and female groups, were significantly higher than those of sexually mature individuals, except when kept in mixed cultures of mature males and females. After mixed-culture, sexually mature males moved significantly further and for a longer duration than mature female abalones, and even more so than mature male abalones of any other group. Examination of the LC-MS metabolomics of mature males cultured with sexually mature females (AM) and those cultured with sexually immature females (JM) showed that cyclic adenosine monophosphate (cAMP) acted as a differential metabolic biomarker. After 24-h uninterrupted sampling, the concentration of 5-HT and the expression levels of the 5-HT2 and 5-HT6 receptors in AM were significantly higher than those in JM. After further injection of 5-HT2 and 5-HT6 receptor antagonists, the concentrations of cAMP and PKA rose again, but the cumulative movement duration and distance of male abalones decreased significantly, showing that 5-HT was involved in the regulation of movement behavior of male abalones through the 5-HT2 and 5-HT6 receptor-activated cAMP-PKA pathways. The results demonstrated a significant increase in the movement endurance of mature male abalones cultured with mature females, providing a theoretical basis for understanding the adaptive life history strategies of abalones and suggesting ways to protect diverse benthic resources for abalones during the reproductive stage.     

Food intake and rumen motility in dwarf goats. Effects of some serotonin receptor agonists and antagonists

The serotonergic regulation of feeding behaviour has not so far been studied in ruminants. Therefore, the effects of some serotonin (5-HT) receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats.Goats ate less food when treated intravenously (IV) with the 5-HT precursor 5-HTP (25 µg, 50 µg or 100 µg kg^–1 min^–1 over 15 min) than when they were treated with 5-HT (which does not pass the blood-brain barrier) or with saline. Accordingly, IV dexfenfluramine infusions (50 µg or 100 µg kg^–1 min^–1 over 15 min), which induces release of brain 5-HT, also led to dose-related reductions in food intake. In contrast, no anorectic effects were observed after IV infusions with the selective 5-HT reuptake inhibitor fluoxetine (100 µg kg^–1 min^–1 over 15 min), the selective 5-HT1A agonist 8-OH-DPAT (0.5 µg kg^–1 min^–1 over 15 min), or eltoprazine (4 or 8 µg kg^–1 min^–1 over 15 min), a mixed 5-HT1A/5HT1B receptor agonist. None of the 5-HT antagonists tested gave any increase in food consumption in this model. Interestingly, the non-selective 5-HT receptor antagonist methysergide (360 µg/kg IV) reduced food intake. This effect was most noticeable at 3 h after injection. The 5-HT3 receptor antagonist ondansetron (IV 10 µg kg^–1 min^–1 over 15 min) and the peripheral 5-HT2 receptor antagonist xylamidine (IV 100 µg kg^–1 min^–1 over 10 min) failed to modify food intake. These results provide evidence for central serotonergic involvement in the control of feeding. However, this control system differs markedly in goats and rodents.Dexfenfluramine, 5-HTP and eltoprazine administered at similar dose rates to those used in the food intake experiments induced some clinical signs including inhibition of forestomach contractions. These results, together with our earlierin vivo andin vitro observations, suggest that the inhibitory effects of serotonin receptor agonists on forestomach contractions are due to interactions with both peripheral and central serotonergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, appears not to modify feeding behaviour in dwarf goats.