目的 相同劑量卵白蛋白和相同激發(fā)時間的條件下，比較豚鼠主動全身過敏反應(yīng)癥狀的嚴(yán)重程度與致敏途徑和激發(fā)途徑的關(guān)系。方法 取300～400 g豚鼠78只，雌雄各半，隨機(jī)分為13組，每組6只。以0.4%卵白蛋白溶液為受試物，氯化鈉注射液為陰性對照，每組動物均隔日致敏1次，連續(xù)致敏3次，致敏劑量為0.5 mL（2 mg/只），末次致敏后第14天各組分別進(jìn)行激發(fā)，激發(fā)劑量為1.0 mL（4 mg/只）。研究不同致敏途徑和激發(fā)途徑條件下，豚鼠主動全身過敏的發(fā)生情況。結(jié)果 在相同致敏劑量、激發(fā)劑量和激發(fā)時間的條件下，均以ip致敏的條件下，豚鼠主動全身過敏反應(yīng)的癥狀嚴(yán)重程度為iv激發(fā) > im激發(fā) > ip激發(fā) > sc激發(fā)；均以im致敏的條件下，癥狀嚴(yán)重程度為iv激發(fā) > ip激發(fā) > im激發(fā) > sc激發(fā)；均以sc致敏的條件下，癥狀嚴(yán)重程度為iv激發(fā) > im激發(fā) > ip激發(fā) > sc激發(fā)；均以iv激發(fā)的條件下，癥狀嚴(yán)重程度為ip致敏 > im致敏 > sc致敏。結(jié)論 新藥主動全身過敏試驗臨床前安全性評價研究應(yīng)注意致敏途徑和激發(fā)途徑。

Objective The relationship between the severity of active systemic anaphylaxis and the sensitization and activation pathways in guinea pigs was compared under the same dose of ovalbumin and the same excitation time. Methods A total of 78 Guinea pigs weighted 300 to 400 grams were randomly divided into 13 groups, each group of six guinea pigs. The 0.4% ovalbumin were used as experimental materials, and sodium chloride injection as negative control, sensitizing once every other day for 3 d, with sensitizing dose of 0.5 ml (2 mg/animal). The excitation was carried out at the fourteenth day after the end sensitization, with challenge dose of 1.0 ml (4 mg/animal). Guinea pigs had active systemic allergic reaction in the study of different sensitizing and challenge way. Results In the conditions of the same sensitizing dose, challenge dose and challenge interval, under the condition of ip sensitization, the severity of guinea pigs' active systemic anaphylaxis was iv excitation > im excitation > ip excitation > sc excitation; Under the condition of im sensitization, the severity of symptoms was iv excitation > ip excitation > im excitation > sc excitation; Under the condition of sc sensitization, the severity of symptoms was iv excitation > im excitation > ip excitation> sc excitation. Under iv stimulation, the severity of symptoms was ip sensitization > im sensitization > sc sensitization. Conclusion Preclinical safety evaluation of the new drug active systemic anaphylaxis should pay attention to the route of sensitization and challenge.