应用清醒大鼠遥测模型评价AF114注射液的心血管系统的安全性

Establishment of a telemetry model in conscious rats for evaluating the cardiovascular safety of AF114 injection

目的:应用可在清醒自由活动状态下长期监测心血管系统参数和体温变化的大鼠遥测模型评价AF114注射液对心血管系统及体温的影响。方法:通过手术将可遥测大鼠血压、心电图、体温的植入体植入大鼠体内,建立清醒大鼠遥测模型。经颈静脉置入导管,经皮下穿刺将导管从颈后侧引出,固定,用于给药或采血。动物术后恢复1周,用阳性药物垂体后叶素验证模型的反应性。验证后用该模型评价AF114注射液对心血管系统及体温的影响。结果:32只大鼠手术后有29只恢复良好,无感染,均可监测到腹主动脉血压、心电图、体温等生理信号。经腹腔注射给予清醒大鼠垂体后叶素1 U.kg-1后,观察到平均动脉压升高,射血时间延长,体温降低,心率减慢。经静脉注射给予AF114注射液后,引起大鼠平均动脉压升高,心率加快,体温升高,对血小板计数和红细胞计数无明显影响。结论:清醒大鼠心血管遥测模型可用于长期、连续、动态监测心血管功能;静脉注射AF114注射液后可引起清醒大鼠血压升高、心率加快和体温升高。

Objective： To establish an animal model that can long-term monitor the cardiovascular parameters and body temperature in conscious and freely moving telemetry rats,and utilizing this model to evaluate the effects of AF114 injection on the cardiovascular parameters and body temperature.Methods： A transmitter body that can monitor BP,ECG,body temperature and activities was implanted in the cavity of the rats.A catheter was inserted in jugular vein for administration of saline and AF114 injection,or for collecting blood samples.After a week recovery,pituitary was used as a positive drug to test the reactivity of the telemetry rat model.Then we utilized this model to evaluate the effect of AF114 injection on the cardiovascular parameters and body temperature.Results： Of the 32 operated rats 29 rats recovered well,and their BP,ECG and body temperature were monitored.The conscious telemetered rat model was successfully established.After ip injection of pituitary 1 U·kg-1 BW,the mean blood pressure was increased,ejection time was prolonged,and body temperature and heart rate were decreased.After iv AF114 injection,the mean blood pressure,heart rate and body temperature were increased.AF114 had no effect on the platelet count and red blood cell count.Conclusion： We have successfully established an animal model that can monitor the cardiovascular parameters and body temperature in conscious and freely moving telemetry rats.AF114 injection can increase blood pressure,heart rate and body temperature in the conscious rats.