大鼠头部暴露全氟异丁烯中毒致肺损伤实验模型的建立

目的：建立大鼠头部暴露吸入染毒致急性肺损伤实验模型以便进行全氟异丁烯(pefluoroisobutylene，PFIB)毒理及防治药物研究。方法：用设计的大鼠头部暴露吸入PFIB染毒装置致动物中毒，测定动物中毒后肺灌流液(BALF)中总蛋白含量和肺湿干比变化，在染毒过程中同时用气相色谱连续监测DFIB浓度。结果：在大鼠头部暴露吸入染毒中，PFIB染毒浓度比较稳定。大鼠吸入PFIB0．18mge／L(8—10min)致肺损伤实验模型比较明显，各项指标变化显著，中毒性肺水肿程度与HFIB浓时积(染毒浓度乘以时间，即CT值)呈正相关，动物中毒后12～24h肺灌流液中总蛋白含量和肺湿干比显著升高。结论：建立了大鼠头部暴露动态吸入PFIB中毒致急性肺损伤实验模型，该模型比较稳定，可用于观察动物PFIB中毒性肺水肿程度，也可作为：PFIB毒理及防治药物研究实验方法。大鼠PFIB中毒途径主要通过呼吸道吸入中毒，其吸入毒性至少比腹腔毒性大10倍。

Acute lung injury induced by rat head-only exposure to PFIB: model establishment

s] Objective: To establish the model of acute lung injury induced by perfluoroisobutylene(PFIB)inhalation through the rats head-only exposure for the study of toxicity and therapeutic chemicals.Methods: PFIB concentration was monifored continuously by gas chromatography in the process of inhalation. The rats were poisoned in the head-only exposure system. To observe acute lung injury,total protein concentration in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were determined after inhalation of PFIB. Results: The exposure concentration of PFIB was relatively stable during the exposure period.The extent of lung weight increase was found to be related to the exposure concentration of PFIB and time of exposure. The optimum dose of PFIB for rats in this exposure system was 0.18 mg/L(8-10 min),not only for the appearance of typical acute lung injury but also for zero death in observation period. Protein concentration in BALF and lung wet/dry weight ratio determined at 12-24 h after PFIB exposure were increased.Conclusion:The model of rat head-only exposure-induced acute lung injury by PFIB of inhalation was established. Inhalation of PFIB seemed to be the main way of inducing pulmonary edema. The toxicity of head-only exposure to PFIB by respiration would be 10 times higher than that by intraperitioneal injection. This model is more stable. It can be used to observe the extent of acute lung injury induced by inhalation of PFIB,as well as to study toxicity of PFIB and therapeutic chemicals.