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

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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 evaluate the effects of AF114 injection on cardiovascular system and body temperature using a rat telemetry model that allows long-term monitoring of cardiovascular system parameters and changes in body temperature under awake free-motion conditions. Methods: The implants of telemetry rat blood pressure, electrocardiogram and body temperature were implanted into rats by surgery, and a telemetric model of conscious rats was established. The catheter is placed in the jugular vein and the catheter is withdrawn from the posterior neck by percutaneous puncture for fixation or blood sampling. Animals were recovered for 1 week postoperatively, and the reactivity of the model was verified with the pituitrin, a positive drug. After validation, the model was used to evaluate the effects of AF114 injection on cardiovascular system and body temperature. Results: Twenty-nine rats recovered well after operation, and no signs of infection were observed. Physiological signals such as abdominal aorta blood pressure, electrocardiogram and temperature were monitored. After intraperitoneal injection of vasopressin 1 U.kg-1 in conscious rats, mean arterial pressure, prolonged ejection time, hypothermia and slow heart rate were observed. Intravenous injection of AF114 injection, causing the average arterial pressure in rats increased heart rate, body temperature, platelet count and red blood cell count had no significant effect. CONCLUSION: The cardiovascular telemetry model of conscious rats can be used for long-term, continuous and dynamic monitoring of cardiovascular function. Intravenous injection of AF114 injection can cause the blood pressure, heart rate and body temperature of conscious rats to rise.
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