目的 研究注射用酒石酸長春瑞濱膠束（NVB-m）對實驗動物中樞神經(jīng)系統(tǒng)、消化系統(tǒng)、心血管和呼吸系統(tǒng)的影響，從而觀察藥物潛在的對生理功能的不良影響，為臨床實驗提供依據(jù)及參考。方法 ①ICR小鼠隨機分為對照組、空白膠束組、地西泮（陽性對照，3 mg/kg）組及NVB-m 4、8、16 mg/m²組和注射用酒石酸長春瑞濱（NVB）16 mg/m²組，單次靜脈推注給藥，通過小鼠自主活動次數(shù)試驗、轉(zhuǎn)棒試驗、協(xié)同睡眠試驗分別對動物的運動功能、協(xié)調(diào)功能、翻正反射進行定量評價，觀察藥物對動物中樞神經(jīng)系統(tǒng)的影響；②ICR小鼠隨機分為對照組、空白膠束組、硫酸阿托品（陽性對照，20mg/kg）組及NVB-m 4、8、16 mg/m²組和NVB 16 mg/m²組，單次靜脈推注給藥，通過觀察墨汁推進率的變化研究藥物對胃腸消化系統(tǒng)的影響；③比格犬隨機分為對照組、空白膠束組及NVB-m 4、8和16 mg/m²組和NVB 16 mg/m²組，單次靜脈推注給藥，多導(dǎo)生理信號記錄儀分別在給藥前、給藥后0.25、0.50、1.00、2.00、4.00、6.00 h各記錄1次心電、血壓和呼吸波形，觀察藥物對動物心血管和呼吸系統(tǒng)的影響。結(jié)果 與對照組比較，NVB-m和NVB組小鼠自主活動未見明顯變化、平衡運動能力未見明顯影響、未見與閾下劑量戊巴比妥鈉協(xié)同睡眠作用；NVB-m組和NVB組小鼠未見墨汁推進率的明顯變化；NVB-m組和NVB組比格犬未見藥物相關(guān)的心電、血壓和呼吸指標(biāo)的明顯變化。結(jié)論 單次靜脈給予16 mg/m²的NVB-m和NVB，未見藥物對實驗動物中樞神經(jīng)系統(tǒng)、消化系統(tǒng)、心血管和呼吸系統(tǒng)產(chǎn)生明顯影響，NVB-m與NVB在相同劑量條件下比較，未見明顯差異。

Objective To research the drug effects on laboratory animals' central nervous system, digestive system, cardiovascular system and respiratory system under the certain dosages thereby observing the potential adverse effects of the drug on physiological functions and providing basis and reference for clinical experiment. Methods ① ICR mice were randomly divided into control group, blank micelle group, diazepam (positive control, 3 mg/kg) group, NVB-m 4, 8 and 16 mg/m² group and NVB 16 mg/m² group. Single intravenous injection was administered. The motor function, coordination function and righting reflex of animals were quantitatively evaluated by the number of spontaneous activities test, rod rotation test and synergistic sleep test, and the influence of central nervous system was observed. ② ICR mice were randomly divided into control group, blank micelle group, atropine sulfate (positive control, 20 mg/kg), NVB-m 4, 8 and 16 mg/m² groups and NVB 16 mg/m² groups. The effects of drugs on gastrointestinal digestive system were studied by observing the change of ink propulsion rate. ③ Beagle dogs were randomly divided into control group, blank micelle group, NVB-m 4, 8 and 16 mg/m² group and NVB 16 mg/m² group. Single intravenous injection was given. The ECG, blood pressure and respiratory waveforms were recorded by multi-channel physiological signal recorder before and after administration 0.25, 0.50, 1.00, 2.00, 4.00 and 6.00 hours respectively. The effects of drugs on cardiovascular and respiratory system were observed. Results No significant changes in spontaneous activities of mice after a single dose of NVB-m and NVB by intravenous injection were found. The balance and exercise abilities of mice showed no impacts. No function together with subthreshold dose of sodium pentobarbital to cause mice sleep were found. No significant changes in gastrointestinal propulsive effect of mice after a single dose of NVB-m and NVB by intravenous injection were found. No significant changes in cardiovascular and respiratory system of beagle dog after a single dose of NVB-m and NVB by intravenous injection were found. Conclusions A single dose of 16 mg/m² of NVB-m and NVB showed no significant influences on laboratory animals' central nervous system, digestive system, cardiovascular system and respiratory system. No significant difference were showed in the same dose of NVB-m and NVB.

國家科技重大新藥創(chuàng)制項目（2015ZX09501004）；天津市科技計劃項目（16PTGCCX00090）