目的 探究補(bǔ)骨脂素、異補(bǔ)骨脂素的急性毒性及兩者（1∶1）混合使用后的相互作用。方法 補(bǔ)骨脂素（1 125、843、633、475 mg/kg）、異補(bǔ)骨脂素（475、404、343、292 mg/kg）以及兩者1∶1的混合物（633、538、457、389、330 mg/kg）1次性ig給予小鼠，連續(xù)觀察并記錄14 d小鼠的毒性反應(yīng)和死亡情況，用SPSS計(jì)算補(bǔ)骨脂素、異補(bǔ)骨脂素以及兩者混合使用后的半數(shù)致死量（LD₅₀），用等效線圖解法判斷兩者的相互作用。結(jié)果 給藥組小鼠均出現(xiàn)僵直、腹部貼地、活動(dòng)力減弱，甚至抽搐、口眼周有分泌物，心率減慢直至死亡的現(xiàn)象，與助溶劑組比較，體質(zhì)量呈降低趨勢(shì)；補(bǔ)骨脂素LD₅₀為638.69 mg/kg，95%可信限為526.91～785.78mg/kg；異補(bǔ)骨脂素LD₅₀為351.72 mg/kg，95%可信限為248.17～394.57 mg/kg；兩者1∶1混合給藥的LD₅₀為454.66 mg/kg，95%可信限為422.58～489.59；兩者合用的LD₅₀在補(bǔ)骨脂素和異補(bǔ)骨脂素相加等效線上。結(jié)論 補(bǔ)骨脂素和異補(bǔ)骨脂素大劑量給予小鼠時(shí)，引起藥物急性毒性反應(yīng)，1∶1混合給藥具有相加作用。

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.

重大新藥創(chuàng)制專項(xiàng)（2014ZX09304307-001-005）；國(guó)家自然科學(xué)基金資助項(xiàng)目（81703790）