目的 探究补骨脂素、异补骨脂素的急性毒性及两者（1∶1）混合使用后的相互作用。方法 补骨脂素（1 125、843、633、475 mg/kg）、异补骨脂素（475、404、343、292 mg/kg）以及两者1∶1的混合物（633、538、457、389、330 mg/kg）1次性ig给予小鼠，连续观察并记录14 d小鼠的毒性反应和死亡情况，用SPSS计算补骨脂素、异补骨脂素以及两者混合使用后的半数致死量（LD₅₀），用等效线图解法判断两者的相互作用。结果 给药组小鼠均出现僵直、腹部贴地、活动力减弱，甚至抽搐、口眼周有分泌物，心率减慢直至死亡的现象，与助溶剂组比较，体质量呈降低趋势；补骨脂素LD₅₀为638.69 mg/kg，95%可信限为526.91～785.78mg/kg；异补骨脂素LD₅₀为351.72 mg/kg，95%可信限为248.17～394.57 mg/kg；两者1∶1混合给药的LD₅₀为454.66 mg/kg，95%可信限为422.58～489.59；两者合用的LD₅₀在补骨脂素和异补骨脂素相加等效线上。结论 补骨脂素和异补骨脂素大剂量给予小鼠时，引起药物急性毒性反应，1∶1混合给药具有相加作用。

Objective To investigate the acute toxicity of the psoralen and isopsoralen, and then explored the interaction between them after mixed use. Methods The different-dose psoralen (1 125, 843, 633 and 475 mg/kg), isopsoralen (475, 404, 343 and 292 mg/kg), and their mixture solution of 1:1 (633, 538, 457, 389 and 330 mg/kg) were ig administrated to the mice, then the toxicity reaction and the mortality of the mice were continuously observed and recorded for 14 days, then LD₅₀ value of them was calculated by SPSS analysis, finally the drug interaction between them was concluded with equivalent diagram method. Results even convulsion, secretion around the mouth and eyes, and slowed heart rate until death All the mice in the treatment group showed rigidity,, abdomen sticking to the ground, weakened activity, even convulsions, secretions around the mouth and eyes, heart rate slowing down until death. Compared with the cosolvent group, the body mass showed a decreasing trend. The LD₅₀ of psoralen was 638.69 mg/kg, and the 95% confidence limit was 526.91 - 785.78 mg/kg; while LD₅₀ of ispsoralen was 351.72 mg/kg, and the 95% confidence limit was 422.58 - 489.59. The LD₅₀ for their mixture of 1:1 was 454.66 mg/kg, and its 95% confidence limit was 422.58 - 489.59. Besides, the LD₅₀ for their mixture was obove the additive equivalent line. Conclusion The acute toxicity of drugs in mice was induced by the megadose of psoralen and isopsoralen., while there was an additive effect with 1:1 mixed of psoralen and isopsoralen.

重大新药创制专项（2014ZX09304307-001-005）；国家自然科学基金资助项目（81703790）