目的 應(yīng)用全身體積描記法觀察藥物對大鼠呼吸指標(biāo)的影響，對動物肺功能檢測系統(tǒng)進(jìn)行性能驗(yàn)證，為該技術(shù)用于藥物安全藥理學(xué)評價提供依據(jù)。方法 SD大鼠30只，雌雄各半，分為溶媒對照組、巴氯芬（30 mg/kg）組、茶堿（30 mg/kg）組，溶媒對照組給予等體積的0.5%羧甲基纖維素鈉溶液。實(shí)驗(yàn)時將動物放入體積描記箱中，動物肺功能檢測系統(tǒng)連續(xù)獲取給藥前至少60 min及給藥后6 h內(nèi)的數(shù)據(jù)，藥后24 h至少連續(xù)采集60 min的數(shù)據(jù)，將每只動物給藥前、給藥后1、2、4、6、24 h均選取連續(xù)平穩(wěn)的30個呼吸波，檢測潮氣量（TV）、每分鐘通氣量（MV）、呼吸頻率（F）。結(jié)果 與溶媒對照組比較，巴氯芬組TV在給藥后1、2、4、6、24 h顯著增大（P<0.05），呈先上升后下降趨勢；F在藥后2、4、6 h顯著減慢（P<0.05），呈先下降后上升趨勢。大鼠給予30 mg/kg的茶堿后呼吸急促，藥后1、2、4 h F明顯加快、MV顯著增加，均呈先上升后下降趨勢，與溶媒對照組比較，藥后1、2 h出現(xiàn)統(tǒng)計學(xué)差異（P<0.05）。結(jié)論 SD大鼠給予巴氯芬和茶堿后呼吸指標(biāo)具有良好時間-反應(yīng)趨勢，可作為陽性藥用于儀器的性能驗(yàn)證；肺功能檢測系統(tǒng)能夠準(zhǔn)確記錄清醒無束縛大鼠呼吸指標(biāo)的變化情況，可用于呼吸系統(tǒng)安全藥理學(xué)研究。

Objective To research the performance qualification of pulmonary function test system with whole-body plethysmography to observe the effect of drugs on rats, and to provide a basis for the future application of this technique for drug safety evaluation. Methods Totally 30 Sprague-Dawley rats were used in this study, 15 males and 15 females. The rats were divided into three groups:solvent control group, baclofen group, and theophylline group. The baclofen and theophylline group received a single dose of 30 mg/kg baclofen or theophylline, and the control group was given an equal volume of 0.5% carboxymethylcellulose sodium solution. In the experiment, rats were placed in a plethysmograph box. The animal lung function test system obtained data at least 60 min before and 6 h after administration. At least 60 min data were collected at least 24 h after administration, and 30 continuous and stable respiratory waves were selected for each animal at 1, 2, 4, 6, and 24 h after administration, and the tidal volume (TV), minute ventilation (MV), and respiratory rate (F) were detected. Results Compared with solvent control group, TV of the baclofen group increased significantly at 1, 2, 4, 6, and 24 h after administration (P<0.05), rising first and then descending; And F decreased at 2, 4, and 6 h after administration, descending first and then rising. F and MV of the theophylline group increased significantly at 1, 2 h after administration (P<0.05), rising first and then descending. Conclusion Based on the good time-response curve, baclofen and theophylline could be used as positive drugs in respiratory safety assessment, for its sensitive and good performance in SD rats. Respiratory signals could be acquired for 6 h continuously in conscious and unrestrained rats accurately with pulmonary function test system, and the system can be used for drug safety pharmacological research of respiratory system.

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