目的 研究醒腦靜注射液對Beagle犬心血管和呼吸系統(tǒng)的影響。方法 已成功埋入植入子的Beagle犬6只，拉丁方設(shè)計(jì)給藥，設(shè)溶媒對照組，輔料對照組，醒腦靜注射液1（XNJI1，含人工麝香）高、中、低劑量（1.41、0.71、0.35 mg/kg）組和醒腦靜注射液2（XNJI2，含天然麝香）高、中、低劑量（1.46、0.73、0.36 mg/kg）組，XNJI1高、中、低劑量均約為人臨床等效劑量的5.2、2.6、1.3倍；XNJI2高、中、低劑量均約為人臨床等效劑量的5.1、2.6、1.3倍。輔料對照組給予等體積的0.5%聚山梨酯80溶液；溶媒對照組給予等體積氯化鈉注射液。前肢iv給藥，每2個(gè)給藥組設(shè)1 d洗脫期。利用DSI遙測系統(tǒng)連續(xù)測量給藥前1 h至給藥后4 h的心電、血壓、呼吸等指標(biāo)。結(jié)果 各給藥組及輔料對照組部分Beagle犬出現(xiàn)明顯過敏癥狀，在給藥后均出現(xiàn)持續(xù)10~45 min的口鼻部發(fā)紅腫脹、瘙癢，部分表現(xiàn)煩躁不安，輔料對照組最為明顯。與溶媒對照組比較，XNJI1高劑量組及輔料對照組心率顯著升高（P<0.05、0.01），分別于給藥后30 min、1 h恢復(fù)至給藥前水平；輔料對照組給藥后5、10、30 min QTc間期顯著延長（P<0.01）；XNJI1高劑量組給藥后10 min、0.5 h呼吸頻率（BPM）顯著升高，XNJI2高劑量組給藥后5 min BPM顯著升高（P<0.05、0.01），輔料對照組給藥后BPM明顯升高但無顯著差異。XNJI1比XNJI2在心率、QTc間期、BPM等方面波動較大，但二者無顯著差異。結(jié)論 給予大劑量醒腦靜注射液，Beagle犬出現(xiàn)不同程度類過敏反應(yīng)癥狀及心電呼吸影響可能與輔料聚山梨酯80有關(guān)，臨床使用應(yīng)密切監(jiān)測相關(guān)指標(biāo)以確保用藥安全。

Objectlve To investigate the effect of Xingnaojing Injection (XNJI) on cardiovascularand respiratory function in Beagle dogs.Methods Six Beagles implanted with implants were setted as vehicle group (normal salin),excipient group (0.5% polysorbate 80) and low (0.35, 0.36 mg/kg), middle (0.71, 0.73 mg/kg), high (1.41, 1.46 mg/kg) dose test groups of sample 1, 2 by Latin square. the dogs were administered intravenously with one day washout period for each two groups. The DSI physiological signal telemetrySystem was used to continuously measure the ECG, blood pressure, and respiration from 1 h before administration to 4 h after administration. Results Some Beagle dogs in each administration group and excipient control group had obvious allergic symptoms, and the mouth and nose redness, swelling and pruritus lasted for 10-45 minutes after administration, and some of them showed irritability and restlessness, especially in the adjuvant control group. Compared with the vehicle control group, the heart rate of XNJI1 high-dose group and excipient control group was significantly increased (P<0.05, 0.01), and returned to the level before administration at 30 min and 1 h after administration; QTc interval at 5, 10 and 30 min in excipient control group was significantly prolonged (P<0.01); respiratory rate (BPM) at 10 min and 0.5 h after administration in XNJI1 high-dose group was significantly increased, and 5 min after administration in XNJI2 high-dose group BPM increased significantly (P<0.05, 0.01), The BPM in the adjuvant control group increased significantly after administration, but there was no significant difference. Compared with XNJI2, XNJI1 fluctuated more in heart rate, QTc interval and BPM, but there was no significant difference between them. Conclusion The anaphyl-actoid symptoms and ECG respiratory effect of XNJI on Beagle dogs were related to polysorbate 80, and the relevant indexes should be monitored closely to ensure the safety ofclinical medication.

R965.3

江蘇省政策引導(dǎo)類計(jì)劃項(xiàng)目［產(chǎn)學(xué)研合作——前瞻性聯(lián)合研究項(xiàng)目（BY2016017-01）］