小鼠周边活动累积数据比率法评价药物镇静效应

Locomotor model based on accumulate peripheral active time percent in ICR mice

目的建立一种基于累积周边活动时间/周边时间的比值(accumulate peripheral active time percent,APATP)的行为学评价模型。方法利用视频跟踪系统检测戊巴比妥钠和地西泮诱导小鼠自发活动并提取相应数据,并计算得到APATP。采用DAS软件对数据进行处理,得到小鼠活动趋稳半衰期((T_1/2)α)、对数曲线下面积(lgAUC0-60)和对数尾点回归值(lgPmin)进行统计学分析。结果各组小鼠的APATP随时间的延长而逐步下降,均符合方程P=Ae-αt+Be-βt。与正常组比较,PB5mg.kg-1组T12α、lgAUC0-60和lgPmin略有下降,而PB10mg.kg-1组(均为P<0.01)和PB15mg.kg-1组(P<0.01,P<0.01和P>0.05)均能不同程度的抑制3参数;与PB10mg.kg-1组比较,PB15mg.kg-1组3参数有所回升(P>0.05,P<0.05和P<0.05)。本模型参数lgAUC0-60和lgPmin与总路程具有较好的一致性(r2=1.0000和r2=0.9995,均为P<0.01)。应用地西泮进一步证实了模型的可行性,具有类似的特点;与正常组比较,地西泮2、4mg.kg-1组3参数均下降(均为P<0.01),认为两组的镇静效应与正常等同;与PB10mg.kg-1比较,地西泮2、4mg.kg-1组的3参数差异均无显著性,认为两组地西泮镇静作用与之等同。结论ICR小鼠累积周边活动时间占比模型可用于评价小鼠自发活动及药物干预效果。

Aim To establish a novel locomotor model based on accumulate peripheral active time percent（APATP）in ICR mice induced by pentobarbital sodium（PB）and diazepam.Methods Total distance,accumulate peripheral active time and accumulate peripheral time were aquired from video tracking system with computer,and APATP in all groups was fit and got correspondent parameters with Drugs Analysis System 2.0.Logarithm of area under the curve（lgAUC0-60）,minimum APATP（lgPmin）,and half time of steady-state locomotor activity（（T_1/2）α）were ready for evaluation.Results APATP decreased with time increasing in all groups gradually,and PB 10 mg·kg-1 and PB 15 mg·kg-1 had similar tendency.PB 10 mg·kg-1 and PB 15 mg·kg-1 all decreased APATP significantly throughout the time course.APATP in all mice was fit to kinetics equation.Compared with norm group,PB 5 mg·kg-1 decreased three parameters slightly（all P0.05）,and PB 10 mg·kg-1 and PB 15 mg·kg-1 had similar tendency.PB 10 mg·kg-1（all P0.05）and PB 15 mg·kg-1（P0.01,P0.01 and P0.05）decreased parameters.Compared with PB 10 mg·kg-1,PB 15 mg·kg-1 increased reversely（P0.05,P0.05 and P0.05）.lgAUC0-60 and lgPmin were both linar with total distance（r2=1.0000 and r2=0.9995,both P0.01）,T12α also showed similar tendcency as well as total distance.Refering PB 10 mg·kg-1 as positive drugs and norm as negative control,diazepam 2 mg·kg-1 and 4 mg·kg-1 depressed all parameters significantly compared with norm group（all P0.01）and were similar as PB 10 mg·kg-1,which indicated that sedative effect of diazepam was the same as PB 10 mg·kg-1.Conclusion Locomotor activity model based on APATP may be used to evaluate drug effects on lomocotor activity induced by sedative hypnotics.