胍丁胺在药物诱发抑郁模型上的药效评价

目的在药物诱发抑郁模型上观察胍丁胺(Agmatine,AG)的抗抑郁作用及可能的作用机制。方法采用小鼠5羟色胺酸(5hydroxytryptophan,5HTP)增强实验,小鼠育亨宾(yohimbine,YOH)毒性增强实验,小鼠阿朴吗啡(apomorphine,APO)诱导体温下降和利血平(reserpine,RES)诱导体温下降实验探讨AG抗抑郁作用及可能的作用环节。用VIDEOMEXV型图像运动解析仪检测小鼠自发活动行为。结果在小鼠5HTP增强实验模型上,单次ig给予AG10～20mg·kg-1剂量,或多次ig给予AG10～80mg·kg-1(qd,连续3d),对5HTP诱导的小鼠甩头行为均具有显著增强作用。在小鼠YOH毒性增强实验模型上,多次ig给予AG10～160mg·kg-1(qd,连续3d),均未见增强YOH毒性作用。在小鼠APO诱导体温下降实验模型上,ig给予AG10～80mg·kg-1(qd,连续7d),对APO16mg·kg-1诱导的降温和AUC0～30均未见显著性的拮抗作用。在小鼠RES诱导体温下降实验模型上,ig给予AG10～80mg·kg-1(qd,连续7d),对RES1mg·kg-1诱导的降温和AUC0～6均有显著的拮抗作用。小鼠ig给予AG10～80mg·kg-1(qd,连续3d)对自发活动无显著性改变。结论AG在药理学抑郁模型有显著的抗抑郁活性。并且其抗抑郁活性与增强5羟色胺(5HT)神经系统功能有关,而与去甲肾上腺素能(NE)神经功能无关。AG在抗抑郁有效剂量范围内无中枢兴奋或抑制性作用。     

中药巴戟天抗抑郁作用的大小鼠模型三级组合测试评价

目的系统评价中药巴戟天的抗抑郁作用.方法中药巴戟天依次用乙醇冷浸和水煎煮提取,得醇提物ME和水煎液;醇提物悬浮于水中依次用氯仿、乙酸乙酯、正丁醇萃取,分别得萃取物ME1（氯仿）、ME2（乙酸乙酯）、ME3（正丁醇）和ME4（水残留）;水煎液经浓缩后用正丁醇萃取,得正丁醇萃取物MW1和水层残留物MW2.通过测试ME、ME1～ME4、MW1和MW2对小鼠自发活动的影响,检测药物的中枢兴奋作用;用小鼠悬尾和大、小鼠强迫游泳等抑郁模型评价药物的抗抑郁作用;利用5-HTP诱导小鼠甩头、APO诱导小鼠刻板、育亨宾致死小鼠等实验,初步解析药物作用的神经系统.结果巴戟天提取物在不影响小鼠自发活动的剂量下显著缩短了小鼠悬尾和大、小鼠强迫游泳等抑郁模型的不动时间,除ME4以外均显著增加了5-HTP诱导的小鼠甩头次数,ME1和ME2同时显著降低了APO诱导的小鼠刻板行为次数,但所有提取物对育亨宾对小鼠的致死作用没有显著影响.结论中药巴戟天主要通过作用于5-羟色胺神经系统来发挥其抗抑郁作用,部分提取物对多巴胺神经系统也有作用.     

积雪草提取物抑制小鼠体外脑单胺氧化酶A的活性

积雪草(ＨｅｒｂａＣｅｎｔｅｌｌａｅｃｕｍＲａｄｉｃｅ)属伞形科(Ｕｍｂｅｌｌｉｆｅｒａｅ)属植物,广泛分布于我国华东、中南及西南地区,具有清热利湿、消肿解毒的功效[1]。现代药理研究表明,积雪草所含的三萜皂苷对大小鼠均有镇静安定作用,在印度传统草药中被广泛用于精神病、癫痫及癔病的治疗。为了解积雪草是否具有抗抑郁作用机制,我们对积雪草提取物影响小鼠体外脑单胺氧化酶Ａ活性的作用进行了研究。1　材料和方法1.1　动物昆明种小鼠,雄性,体重20～26ｇ,由本院实验动物中心提供。1.2　试药积雪草提取物为灰白色粉剂,由本所植化室…     

5-HT_（1A）受体激动和5-HT重摄取抑制双靶标新药YL-0919抗抑郁作用的药效学评价

目的评价兼有5-HT1A受体激动和5-HT重摄取抑制双靶标化合物YL-0919的抗抑郁作用,并在靶标水平探讨其作用机制。方法和结果在小鼠悬尾和小鼠强迫游泳实验中,YL-0919（1.25,2.5,5 mg/kg,ig）能够显著地缩短小鼠悬尾不动时间和游泳不动时间,5-HT1A受体拮抗剂WAY100635（0.3 mg/kg,sc）能够完全拮抗YL-0919（2.5 mg/kg,ig）在小鼠悬尾实验中的抗抑郁作用;在药物诱发抑郁模型上,YL-0919增强5-羟色氨酸（5-hydroxytryptophan,5-HTP,120 mg/kg,ip）诱导的小鼠甩头行为,但不能拮抗高剂量阿扑吗啡（16 mg/kg,sc）诱导的降温作用;YL-0919在抗抑郁有效剂量范围内对小鼠的自主活动性无显著性影响。结论新型双靶标新药YL-0919具有明确的抗抑郁作用,此作用与激动5-HT1A受体,增强5-HT系统的功能有关。     

米塔扎平和帕罗西汀的新剂型的药理学和临床评价

米塔扎平主要通过增加去甲肾上腺素和5-羟色胺神经递质的释放产生抗抑郁和抗焦虑的作用,口服崩解型的米塔扎平具有与普通米塔扎平胶囊相同的生物效应,而且能明显增加患者的依从性,有望成为传统剂型的替代品.帕罗西汀的作用机制是抑制5-羟色胺的再摄取,增强5-羟色胺的传递效能.帕罗西汀控释片能很好地控制药物的释放速度,减少血浆药物浓度的波动,具有明显的抗抑郁效果.低剂量的帕罗西汀控释片能降低不良反应的发生,提高长期用药的耐受性.     

多巴胺D_3受体拮抗剂Y-QA14抗精神分裂症作用的初步研究

目的研究多巴胺D3受体拮抗剂Y-QA14对精神分裂症的药理学作用。方法采用甲基苯丙胺（0.5mg/kg,i.p.）和MK-801（0.25mg/kg,i.p.）诱发高活动性、阿扑吗啡（2mg/kg,s.c.）诱发攀爬、5-羟色胺酸（5-HTP,150mg/kg,i.p.）诱发甩头等模型,评价Y-QA14潜在的抗精神分裂症作用。结果 Y-QA14（5,10,15mg/kg）本身影响小鼠自发活动不显著（P〉0.05）,但能抑制甲基苯丙胺（P〈0.01）和MK-801诱发的小鼠高活动性（P〈0.05）。Y-QA14（5,10,20mg/kg）抑制阿扑吗啡诱发的攀爬（P〈0.05）及5-HTP诱发的甩头（P〈0.001）。结论 Y-QA14对精神分裂症可能具有一定的治疗作用。     

纳络酮对铝中毒小鼠学习记忆障碍的改善作用

在口服氯化铝导致学习记忆障碍模型的基础上,用跳台、避暗等实验方法观察了纳络酮对铝中毒小鼠学习记忆障碍的改善作用,并测定了肝丙二醇、脑B型单胺氧化酶的变化。实验结果显示,氯化铝可导致小鼠学习记忆障碍,以及增高丙二醛和B型单胶氧化酶的作用,而纳络酮对改善铝中毒小鼠学习记忆障碍有作用,同时有清除过氧化脂质和抑制B型单胶氧化酶活性的作用。     

玄参中苯丙素苷Acteoside对小鼠高尿酸血症的影响

目的探讨玄参中苯丙素苷Acteoside对小鼠高尿酸血症的影响及可能的作用机理。方法从玄参根中分离提取苯丙素苷成分Acteoside,采用次黄嘌呤造成小鼠高尿酸血症,观察Acteoside对小鼠高尿酸血症的影响,并进一步从体外观察Acteoside对黄嘌呤氧化酶的抑制作用。结果Acteoside能显著降低高尿酸血症小鼠体内的尿酸水平,体外实验显示其对黄嘌呤氧化酶有明显的抑制作用,IC50为12.25μgml-1。结论玄参中Acteoside在小鼠高尿酸血症中的降尿酸作用可能与其抑制黄嘌呤氧化酶作用有关。     

葛胺酮对在体和离体动物脑动脉舒张作用的研究

目的研究葛胺酮对在体和离体动物脑动脉的舒张作用。方法在体实验采用激光多普勒血流仪,连续动态观察葛胺酮对正常大鼠脑血流灌注压、血压(收缩压、舒张压、平均动脉压)、心率、心电图指标的的影响。体外实验采用分离犬基底动脉条,分别以重酒石酸去甲肾上腺素(5 mg·L-1),KCl(3 mol·L-1),5-羟色胺(3.3 mg·L-1)收缩效应的百分率作为评价抑制强度的指标,研究葛胺酮对基底动脉的舒张作用强度及特点。结果在体实验观察到葛胺酮25、50、100 mg·kg-1对大鼠脑血流量灌注压均有增加作用,100 mg·kg-1组比给药前脑血流增加了2～3倍。葛胺酮在增加脑血流量的同时对收缩压、舒张压均有短暂的降压作用,舒张压下降幅度大于收缩压,平均血压下降了10～40 mmHg。体外实验发现葛胺酮0.01、0.1 mg·ml-1对重酒石酸去甲肾上腺素、KCl、5-羟色胺诱导的犬基底动脉收缩均有明显的抑制作用,其舒张率达21%～99%。结论葛胺酮具有增加脑血流量同时降低血压的作用,优于葛根素。其增加脑血流量的作用与其舒张动脉的作用有关。葛胺酮可能是一个多靶点的血管紧张抑制剂,对脑缺血可能具有一定的保护作用,值得进一步研究。     

两种黄花菜组方抗抑郁作用的行为特征比较

目的用经典、快速的抗抑郁药物筛选方法比较两种黄花菜组方——欣宁颗粒、欣安颗粒的抗抑郁作用,为寻找防治航天特因环境引起抑郁的潜在药物。方法雄性ICR小鼠接受欣宁颗粒低、中、高剂量和欣安颗粒低、中、高剂量灌胃给药,以帕罗西汀作为阳性对照药,连续给药21 d。采用小鼠空场实验(OFT)、悬尾实验(TST)和强迫游泳实验(FST)等行为学测试评价欣宁颗粒和欣安颗粒的抗抑郁活性;采用利血平拮抗实验评价欣宁颗粒和欣安颗粒对单胺能神经系统功能的影响。结果空场实验结果显示,欣宁颗粒和欣安颗粒不影响小鼠的运动活性。欣宁颗粒中、高剂量组可以明显减少小鼠在悬尾实验中的不动时间(P0.05,P0.01)。强迫游泳实验中,欣宁颗粒低、中、高剂量组均可显著降低小鼠不动时间(P0.05)。在利血平拮抗实验中,与模型组相比,欣宁颗粒中、高剂量(P0.01)和欣安颗粒高剂量(P0.01)可拮抗利血平引起的小鼠眼睑下垂,欣宁颗粒中剂量(P0.01)和欣安颗粒低剂量(P0.01)可拮抗利血平引起的小鼠的体温下降。结论两个组方相比,欣宁颗粒具有较好的抗抑郁疗效,其机制可能与增强单胺能系统的功能有关。     

Exercise intervention may prevent depression

Physical activity is an effective component of depression management. However, the mechanisms by which exercise affects behavioral disorders remain unclear. The present study was conducted to investigate mechanisms by which voluntary exercise ameliorates depression. Plasma cortisol levels and hippocampal monoamine neurotransmitters were measured. Chronic mild stress (CMS) was used to induce depression in a rat model. The rats were allowed to swim for 10 weeks as part of their exercise treatment. Depressive behavior was analyzed using an open-field test and a sucrose consumption test before and after exercise. Serum cortisol levels were measured by radioimmunoassay. The concentrations of monoamine neurotransmitters in the hippocampus were determined using high-performance liquid chromatography with electrochemical detection. The CMS rats showed behavioral improvement after exercise. Compared with the control, serum cortisol levels were significantly increased by CMS. The serotonin, dopamine, and norepinephrine levels in the hippocampi were significantly increased by exercise. These findings indicate that exercise reverses and prevents the decrease in serotonin and noradrenaline, and restores dopamine in the CMS model.     

遍地金提取物对大鼠脑突触体单胺氧化酶抑制作用评价

目的：评价遍地金提取物对大鼠脑突触体单胺氧化酶的抑制作用。方法：通过大鼠脑突触体单胺氧化酶的抑制实验，测定其重摄取量cpm及抑制百分率。结果：遍地金提取物组平均抑制百分率为93．0％，IC50=269．15mg／ml。St．John's Wort组平均抑制百分率为93．0％，IC50=71．00mg／ml。结论：遍地金提取物与在欧美上市的抗抑郁药物St．John's Wort均能抑制大鼠脑突触体单胺氧化酶的活性，二者差异无统计学意义。     

口服异烟肼对肺结核病人血清单胺氧化酶的影响

测定了服异烟肼（INH）的肺结核病人121例，在服药前后血清中单胺氧化酶（MAO）的水平。结果表明：服药后血清MAO水平较服药前明显降低（P＜0．01），其中以服INH3个月组血清MAO水平最低。本文证实血清MAO水平的降低与病人性别、年龄及INH乙酰化类型无关。     

胍丁胺抑制中枢不同脑区单胺类神经递质释放

目的：观察胍丁胺对吗啡依赖大鼠不同脑区脑片单胺类神经递质戒断释放的抑制作用。方法：用ＨＰＬＣ法测定脑片单胺类神经递质浓度。结果：纳洛酮能使吗啡依赖大鼠出现戒断综合征;使其海马、纹状体和丘脑脑片单胺类神经递质释放增加。用胍丁胺和吗啡共同处理大鼠,纳洛酮的上述作用显著受到抑制。胍丁胺的此项药理作用可被咪唑克生阻断。结论：胍丁胺通过激活咪唑啉受体,抑制纳洛酮引起的吗啡依赖大鼠不同脑区单胺类神经递质释放,胍丁胺的此项作用与其抑制戒断综合征相关。     

Dominant lethals following acute spermatogonial X-irradiation in the rat.

Spermatogonial X-irradiation with 0, 400 or 600 R in adult rats and 200 R in fetal rats was carried out to assess genetic damage by the test of induced dominant lethality. From postimplantation embryonic losses observed, dominant lethal rates were established to be significantly raised by a dose of 400 or 600 R. With 200 R given either to adult or to fetal rats, no excess was detected in embryonic death rates.     

耐力训练对饮食性肥胖鼠下丘脑单胺类递质的影响

为研究饮食性肥胖鼠下丘脑单胺类神经递质含量和肥胖的关系，以及耐力训练对其影响，选用４４只雄性离乳ＳＤ大鼠，３６只饲以高脂饲料，其余为对照。１０周后，高脂组１８只鼠确定为饮食诱发肥胖大鼠（ＤＩＯ），其中８只用跑台进行耐力训练（６５－７５％Ｖｏ２ｍａｘ）。所有大鼠继续饲养８周后处死。所有大鼠记录能量摄入，以高效液相色谱法测定下丘脑单胺类神经递质。结果如下：肥胖鼠不存在多食，下丘脑ＮＥ、ＤＡ和５－ＨＴ增加。耐力运动可以提高下丘脑ＮＥ含量。提示，下丘脑单胺类神经递质的改变可能与高脂饮食的能量密度高有关。耐力训练可有效地降低饮食性肥胖鼠体脂，但并不是通过下丘脑单胺类神经递质的调节作用实现的。     

The use of gelatine in wound ballistics research

Blocks of gelatine are used in both lethality and survivability studies for broadly the same reason, i.e. comparison of ammunition effects using a material that it is assumed represents (some part of) the human body. The gelatine is used to visualise the temporary and permanent wound profiles; elements of which are recognised as providing a reasonable approximation to wounding in humans. One set of researchers aim to improve the lethality of the projectile, and the other to understand the effects of the projectile on the body to improve survivability. Research areas that use gelatine blocks are diverse and include ammunition designers, the medical and forensics communities and designers of ballistic protective equipment (including body armour). This paper aims to provide an overarching review of the use of gelatine for wound ballistics studies; it is not intended to provide an extensive review of wound ballistics as that already exists, e.g. Legal Med 23:21–29, 2016. Key messages are that test variables, projectile type (bullet, fragmentation), impact site on the body and intermediate layers (e.g. clothing, personal protective equipment (PPE)) can affect the resulting wound profiles.

     

When backyard fun turns to trauma: risk assessment of blunt ballistic impact trauma due to potato cannons

Although potato cannons are an area of great interest among internet users, they are almost completely unknown in the medical community. These simple ballistic devices are made from plastic plumbing pipes and are powered with propellant gas from aerosol cans. By combustion of the gas–oxygen mixture, a high pressure is produced which propels the potato chunks through the barrel. It is the aim of this study to investigate the hazardous potential of these shooting devices. Test shots were performed using three illegally manufactured potato cannons that were confiscated by police authorities. Velocity, impulse, kinetic energy, and energy density were calculated. The risk of head and chest injuries was investigated by using Sturdivan's Blunt Criterion (BC), an energy based five parametric trauma model assessing the vulnerability to blunt weapons, projectile impacts, and behind-body-armor exposures. The probability of lethality due to blunt impact trauma to the chest was assessed using Sturdivan's lethality model. For potential head impacts, all test shots far exceeded the critical BC (head) value which corresponds to a 50% risk of skull fracture. The risk of injury with regard to chest impacts was similar. All but two test shots far exceeded the critical BC (chest) value corresponding to a 50% risk of sustaining a thoracic skeletal injury of Abbreviated Injury Scale 2 or 3. The probability of a lethal injury due to blunt chest impact was as high as 20%. To conclude, this work demonstrates that potato cannons should be considered dangerous weapons rather than as toys used by adventurous adolescents.     

氨基酸复方制剂对晕船大鼠脑干单胺类递质含量的影响

目的 了解由支链氨基酸和酪氨酸组成的复方制剂对模拟晕船后大鼠脑干单胺类递质的影响.方法 给大鼠饲料分别添加支链氨基酸和由酪氨酸和支链氨基酸组成的复合制剂喂养10 d,大鼠经模拟晕船刺激后,应用高效液相色谱法检测脑干单胺类递质含量的变化.结果 与空白组相比,大鼠模拟晕船刺激后,去甲肾上腺素(NE)和肾上腺素(E)含量降低,5-羟色胺(5-HT)的含量升高;与晕船组相比,给予支链氨基酸后,NE的含量无明显变化,E的含量升高,而5-HT的含量降低;给予支链氨基酸和酪氨酸的复方制剂后,脑干5-HT含量显著降低,NE和E的含量显著升高.结论 氨幕酸制剂可改变模拟晕船大鼠脑干单胺类递质的含量,并通过单胺类递质含量变化影响晕船后的脑体功能.