注射用灯盏花素Beagle犬和小鼠安全药理学差异性研究  

Difference in safety pharmacology of Breviscapine injection between mice and Beagle dogs

作　　者：谢琛静[1] 骆永伟[1] 王蓉[1] 王永[1] 陈颖[1] 桂博[1] 周莉[1] 孙祖越[1] 

机构地区：[1]上海市计划生育科学研究所药理毒理学研究室中国生育调节药物毒理检测中心,上海200032

出　　处：《中南药学》2015年第5期458-464,共7页Central South Pharmacy

基　　金：国家"重大新药创制"科技重大专项(编号:2011ZX09301-005);上海市"科技创新行动计划"实验动物研究项目(编号:14140901302)

摘　　要：目的观察注射用灯盏花素对Beagle犬呼吸系统、心血管系统以及ICR小鼠协调功能和自发活动的影响,考察药物可能关系到人安全性的非期望药理作用。方法 24只Beagle犬雌雄各半,按体重随机分为10、30、90 mg·kg-1和溶媒对照组,每组6只,平行测定动物给药前和给药后2 min、30 min、1 h、2 h及4 h的心电图、呼吸、血压及肛温;ICR小鼠80只雌雄各半,其中40只按体重随机分为10、100、500mg·kg-1和溶媒对照组,分别尾静脉给予不同剂量注射用灯盏花素后观察动物机体协调能力;另外40只同样分组测定给药后不同时间点的小鼠自发活动次数。结果相同时间点各剂量组与溶媒对照组及给药前自身比较发现,Beagle犬心电指标、体温、收缩压、舒张压和平均动脉压均有一定程度的波动,但差异无统计学意义(P>0.05)。ICR小鼠给药后高剂量组出现闭眼和运动减少等反应,1 h左右恢复正常;与溶媒对照组比较,各组动物协调功能差异没有统计学意义(P>0.05),高剂量组雌雄小鼠给药后2 min和30min自发活动次数均有下降的趋势,雌鼠给药后2 min自发活动次数明显减少(P<0.05)。结论在本实验条件下,单次静脉给予注射用灯盏花素对Beagle犬的呼吸、心血管系统及体温无明显影响。单次给予注射用灯盏花素对小鼠协调功能无明显影响,500 mg·kg-1注射用灯盏花素对雌性小鼠在2 min时会产生一过性的轻度躯体运动障碍或中枢抑制作用。Objective To observe the effect of Breviscapine injection on the respiratory and cardiovascular system in Beagle dogs and the coordination function and spontaneous activity in ICR mice, and consider the unexpected pharmacological effects of Breviscapine related to human safety. Methods Totally 24 Beagle dogs （12 males and 12 females） were randomly divided into 10, 30, and 90 mg kg-1 subgroups and a control group according to their weight. Each group had 6 dogs. Electrocardiogram （ECG）, respiration, blood pressure and rectal temperature were measured （parallel determination） before and 2 min, 30 min, 1 h, 2 h and 4 h after Breviscapine injection; 80 ICR mice （40 males and 40 females） were randomly divided into 2 groups： the first group with 40 mice （20 males and 20 females） were randomly divided into 10, I00, and 500 nag ~ kg ~ subgroups and a control group according to their weight. The coordination function was observed after injecting different dosages of breviseapine. With the same method, spontaneous activities were observed in the second group of the other 40 mice. Results Before and after the administration, the experimental groups and the control group were compared. The ECG, temperature, systolic pres- sure, diastolic pressure and mean arterial pressure did not fluctuate in the Beagle dogs significantly （P 〉 0.05）. The results were consistent before and after the administration in all groups. Eye close and reduced movement were found in the high dosage group of ICR mice, and the symptoms disappeared after 1 h. Compared with the control group, no statistical significance （P ~ 0.05） was found in the coordination function. There was a decline in the spontaneous activities in both male and female mice in the high dosage groups 2 rain and 30 min after the injection, while female rice significantly reduced the spontaneous activity （P ~ 0.05） 2 min after the injection. Conclusion No significant ef- fect of Breriscapine injection on the respiratory and the cardiovascular syste

关 键 词：注射用灯盏花素 小鼠 BEAGLE犬 安全药理学 差异性 

分 类 号：R285.5[医药卫生—中药学]