注射用利培酮微球的作用机制及临床应用

注射用利培酮微球是第一个非典型抗精神病药长效剂型,于2006年进入我国市场。它采用先进的Med isorb(微球体)专利技术,减少了首过效应,提高了生物利用度,减少了吸收和生物代谢的个体差异;其在体内缓慢均匀释放的特性,使患者能保持稳定的稳态血浆药物浓度,即便长期治疗中漏掉1次注射,体内药物也不会突然中断;该药物临床疗效好、不良反应少、安全性高,使患者有较好的依从性,且具有最佳的成本-疗效效益。文中综述了注射用利培酮微球的药动学、药效学、临床疗效、安全性及药物经济学效益的最新研究进展。     

地卓西平马来酸盐对雄性大鼠自发活动和前脉冲抑制及再认记忆的影响

目的 观察急性腹腔注射N-甲基-D-天冬氨酸(NMDA)受体拮抗剂地卓西平马来酸盐(MK-801)刘大鼠自发活动、感觉运动门控和物体再认记忆的影响,探讨MK-801模拟精神分裂症不同内表现型的适宜剂量.方法 成年雄性SD大鼠共104只,按照体质量采用分层随机化方法进行分组.(1)取SD大鼠48只,分为MK-801小剂量组、MK-801中剂量组、MK-801高剂量组和对照组,每组12只,观察不同剂量MK-801 (0.1、0.2、0.4 mg/kg)对大鼠自发活动的影响;(2)取SD大鼠32只,分为MK-801小剂量组、MK-801中剂量组、MK-801高剂量组和对照组,每组8只,观察不同剂量MK-801(0.1、0.2、0.4 mg/kg)对大鼠前脉冲抑制(PPI)的影响;(3)取SD大鼠24只,分为MK-801小剂量组和对照组,每组12只,观察小剂量MK-801 (0.1 mg/kg)对大鼠物体辨别测试的影响.结果 (1)中高剂量MK-801 (0.2,0.4 mg/kg)呈剂量依赖性诱导大鼠自发活动的增加以及PPI的损害(P＜0.05或P＜0.01),小剂量(0.1 mg/kg)组在自发活动和PPI上与对照组差异无统计学意义(P＞0.05).(2)小剂量MK-801组在物体辨别测试中对新物体的偏爱指数显著低于对照组[(57.79±10.66)％比(73.34±18.52)％,P＜0.05].结论 中高剂量MK-801可引起自发活动和感觉运动门控功能异常,而小剂量在排除运动系统异常的前提下可特异性地破坏大鼠的再认记忆,提示MK-801模拟精神分裂症的不同内表现型时应根据研究目的选择适宜剂量.     

氟哌啶醇对MK-801致小鼠高活动性与前脉冲抑制损害的作用

目的观察氟哌啶醇对谷氨酸功能低下小鼠模型表现出的高活动性及前脉冲抑制(prepulse inhibition,PPI)损害的作用。方法昆明种小鼠152只分组(n=8或n=10)进行下述对照观察:观察不同剂量氟哌啶醇(0.03、0.1、0.3 mg/kg)腹腔注射对昆明种小鼠探究行为和自主活动的影响;以0.25 mg/kg MK-801诱导小鼠自主活动增加,观察上述剂量氟哌啶醇对MK-801致小鼠高活动性的影响;以0.5 mg/kg MK-801诱导小鼠PPI损害,观察氟哌啶醇(0.1、0.3、1 mg/kg)对基线水平PPI以及MK-801损害后PPI的作用。结果与对照组比较,氟哌啶醇剂量为0.1 mg/kg和0.3 mg/kg时,小鼠的探究行为及自主活动总路程减少(P<0.05);但剂量为0.03 mg/kg时,对小鼠的探究行为及自主活动均无影响(P>0.05)。氟哌啶醇剂量为0.1~0.3 mg/kg时,呈剂量依赖性抑制由MK-801引起的自主活动增加(F=27.23,P<0.01),0.1mg/kg的氟哌啶醇的抑制程度为22%(P<0.01),0.3 mg/kg的氟哌啶醇的抑制程度为65%(P<0.00...     

小剂量MK-801对大鼠参照记忆、空间工作记忆和逆反学习能力的影响

目的 探讨腹腔注射N-甲基-D-天冬氨酸 (NMDA )受体拮抗剂地卓西平马来酸盐(MK-801)对大鼠认知功能的影响.方法 成年雄性SD大鼠随机分为MK-801组和对照组,分别腹腔注射小剂量生理盐水或MK-801(0.1 mg/kg)20 min后在Morris水迷宫中评定MK-801对大鼠参照记忆、空间工作记忆和逆反学习能力的影响.结果 参照记忆任务中,与对照组相比MK-801组逃避潜伏期延长(P<0.05),且在目标象限的探索时间百分比[(22.7±2.9)%]与相邻象限[(24.0±0.9)%]和对立象限[(29.3±2.4)%]的差异无统计学意义 (P>0.05);空间工作记忆任务中,对照组匹配试次潜伏期显著短于样本试次[(37.6±6.0) vs (61.5±6.3),P<0.05],而MK-801组两试次潜伏期差异无统计学意义[(53.8±7.8) vs (62.2±7.1),P>0.05];逆反学习任务中,与对照组相比MK-801组潜伏期明显延长(P<0.05),且在空间探索中新旧目标象限探索时间百分比差值小于对照组[(-0.01±4.7) vs (23.5±6.2),P<0.01].结论 腹腔注射小剂量MK-801破坏了大鼠的参照记忆、空间工作记忆和逆反学习,提示其在多个认知维度上可模拟精神分裂症患者的认知缺陷.     

奥氮平对谷氨酸功能低下的精神分裂症小鼠模型的作用

Objective To investigate the effects of olanzapine on hyperlocomotion and deficient prepusle inhibition (PPI) of hypoglutamatergic schizophrenia model in mice produced by dizocilpine maleate (MK-801), an N-methyl-D-aspartate (NMDA)antagonist.Methods (1) To investigate the effects of olanzapine on explorative behavior and spontaneous activity, three doses of olanzapine ( 0.1, 0.2, 0.3 mg/kg, i.p.) or vehicle was injected 30 min before the test.Locomotor activity was recorded for 30 min with an automated video tracking system, in which the components of the locomotor activity were divided into exploration (the first 10 min) and spontaneous activity (the second 20 min).(2) To examine the effects of olanzapine on MK-801-induced hyperlocomotion, mice were administered with olanzapine (0.1, 0.2 and 0.3 mg/kg) or vehicle 5 min before administration of MK-801 (0.25 mg/kg).After the second injection, locomotor activity was recorded for 90 min by the video tracking system.( 3 ) To explore the effects of olanzapine on intact and MK-801-disrupted sensorimotor gating, olanzapine (0.3, 1,3 mg/kg, i.p.) or the vehicle were injected 35 min before the start of the experiment, MK-801 (0.5 mg/kg, i.p.) or the same volume of saline was administered 5 min before the PPI experiment.Results ( 1 ) Olanzapine (0.2 and 0.3 mg/kg) significantly inhibited the explorative behavior and spontaneous activity (P ＜ 0.05 ) .Olanzapine at 0.1 mg/kg did not affect exploration ( P = 0.363 ) and spontaneous activity ( P = 0.196 ).Olanzapine (0.1 - 0.3 mg/kg) dose-dependently antagonized MK-801 -induced hyperlocomotion.(2) None of the olanzapine doses tested had a significant effect on baseline PPI.Olanzapine ( 1 - 3 mg/kg) dosedependently restored the MK-801-induced deficits in PPI.Conclusion Olanzapine specifically inhibited the MK-801-induced hyperlocomotion and deficits in PPI in mice and the results are also consistent with clinical findings.     

p53调控的能量代谢对辐射效应的影响

p53基因一直是肿瘤病因学、放射生物学的研究热点,但受其调控的能量代谢在辐射生物效应中的作用还存在许多未知因素.了解p53基因调控的能量代谢对探讨肿瘤放射治疗疗效、辐射损伤、辐射致癌的早期筛选生物指标和分子流行病学调查均有着极其重要的意义.该文概述了此方面的研究进展.     

奥氮平对谷氨酸功能低下的精神分裂症小鼠模型的作用

Objective To investigate the effects of olanzapine on hyperlocomotion and deficient prepusle inhibition (PPI) of hypoglutamatergic schizophrenia model in mice produced by dizocilpine maleate (MK-801), an N-methyl-D-aspartate (NMDA)antagonist.Methods (1) To investigate the effects of olanzapine on explorative behavior and spontaneous activity, three doses of olanzapine ( 0.1, 0.2, 0.3 mg/kg, i.p.) or vehicle was injected 30 min before the test.Locomotor activity was recorded for 30 min with an automated video tracking system, in which the components of the locomotor activity were divided into exploration (the first 10 min) and spontaneous activity (the second 20 min).(2) To examine the effects of olanzapine on MK-801-induced hyperlocomotion, mice were administered with olanzapine (0.1, 0.2 and 0.3 mg/kg) or vehicle 5 min before administration of MK-801 (0.25 mg/kg).After the second injection, locomotor activity was recorded for 90 min by the video tracking system.( 3 ) To explore the effects of olanzapine on intact and MK-801-disrupted sensorimotor gating, olanzapine (0.3, 1,3 mg/kg, i.p.) or the vehicle were injected 35 min before the start of the experiment, MK-801 (0.5 mg/kg, i.p.) or the same volume of saline was administered 5 min before the PPI experiment.Results ( 1 ) Olanzapine (0.2 and 0.3 mg/kg) significantly inhibited the explorative behavior and spontaneous activity (P ＜ 0.05 ) .Olanzapine at 0.1 mg/kg did not affect exploration ( P = 0.363 ) and spontaneous activity ( P = 0.196 ).Olanzapine (0.1 - 0.3 mg/kg) dose-dependently antagonized MK-801 -induced hyperlocomotion.(2) None of the olanzapine doses tested had a significant effect on baseline PPI.Olanzapine ( 1 - 3 mg/kg) dosedependently restored the MK-801-induced deficits in PPI.Conclusion Olanzapine specifically inhibited the MK-801-induced hyperlocomotion and deficits in PPI in mice and the results are also consistent with clinical findings.     

酒精戒断状态评定量表中文译本的效度和信度测试

目的 评价酒精戒断状态评定量表(AWS)中文译本的信度和效度.方法 选取175例符合ICD-10诊断标准的酒精依赖患者为研究对象,进行AWS量表评定,计算组内相关系数(ICC)评价评定者间一致性;计算克朗巴赫α系数评价量表内部一致性;采用主成份分析方法计算条目的因子负荷考评量表结构效度;通过AWS与临床总体印象量表(CGI)以及CIWA-Ar(CIWA-Ar)的相关分析来评价量表的效标效度;以临床标准为参考标准,根据ROC曲线下面积(Area Under Curve,AUC)来判断量表的区分效度以及划定量表的划界分.结果 (1)信度:评定者一致性ICC为0.93;量表总克朗巴赫α系数为0.83.(2)效度:AWS量表与两个分量表之间相关系数为0.78,0.83,两个分量表之间的相关系数为0.81,通过因子分析,量表的每个条目都在主因子上有较高的负荷值(0.409～0.926);入院时AWS总分与CGI评分严重程度呈显著正相关(r=0.71,P<0.05),与CIWA-Ar总分呈正相关(r=0.86,P<0.05).随治疗进行,AWS总分呈减分趋势,治疗第1周结束时AWS与CGI疗效评分呈显著相关(r=0.62,P<0.05).以临床评估标准为参考在区分轻度戒断状态时界值分为≥3时灵敏度特异度最好,分别为92.1%和73.5%,AUC为0.91,区分中度戒断状态时AWS总分≥7分灵敏度特异度最高,分别为94.3%,89.7%,AUC为0.94;在区分重度戒断状态时AWS总分≥10分灵敏度特异度最高,分别为94.9%,92.6%,AUC为0.93.结论 AWS中文译本具有较好的信度和效度,能够区分戒断状态的严重程度及反映治疗的疗效.     

快感缺失相关的精神分裂症阴性症状动物模型的研究

目的在精神分裂症NMDA受体功能低下神经发育假说基础上,建立快感缺失相关的精神分裂症阴性症状动物模型。方法将新生大鼠随机分6组,每组8～10只,NS-NS组,NS-HAL(氟哌啶醇)组,NS-RIS(利培酮)组,MK801-NS组,MK801-HAL组,MK801-RIS组。大鼠出生后第5～14天分别给予生理盐水及MK-801,在大鼠成年期给予抗精神病药利培酮及氟哌啶醇干预,亚慢性给药2周后进行糖水实验,检测糖水消耗量及糖水偏爱度。结果新生期暴露于MK-801的动物糖水偏爱度(0.63±0.046)显著低于对照组(0.838±0.047),P0.05,利培酮干预组动物的糖水偏爱度(0.86±0.060)显著高于氟哌啶醇干预组(0.631±0.055),P0.05。结论新生期暴露于NMDA受体拮抗剂MK-801可导致动物出现快感缺失,利培酮可逆转该损害。NMDA受体功能低下神经发育模型可作为快感缺失相关的精神分裂症阴性症状动物模型。     

应激对大脑的差异性影响及其意义

正应激,是指机体在内环境遭到破坏时或者对预期威胁信号所做出的非特异适应性反应。机体的应激反应主要依赖于交感—肾上腺髓质系统和下丘脑—垂体—肾上腺皮质(hypothalamic-pituitary-adrenocortical,HPA)系统的调控。在生命的各个阶段,暴露于应激都可能会对大脑的结构以及精神健康产生影响。这种特定影响主要与遭受应激的生命阶段(发育阶段)、应激强度、持续时间以及早年的