欧前胡素急性毒性和安全药理学研究

Pharmacology studies on acute toxicity and safety of imperatorin

目的观察欧前胡素对大、小鼠的急性毒性,以及对小鼠神经系统和犬心血管系统、呼吸系统的影响。方法通过腹腔内注射给药(ip)和灌胃给药(ig)研究欧前胡素对小鼠的急性毒性,以及ig对大鼠的急性毒性实验。安全药理学实验中以50、100、200 mg/kg分别单次ig给予小鼠欧前胡素,观察对小鼠神经系统的影响(包括小鼠自发活动、爬杆能力、小鼠阈下剂量戊巴比妥钠催眠协同实验);以25、50、100 mg/kg分别单次口服给药(po)欧前胡素,观察对犬心血管系统和呼吸系统的影响(包括心电图、血压、心率,以及呼吸频率、幅度、节律等指标)。结果欧前胡素ig对小鼠的LD_(50)为988.5 mg/kg;ip对小鼠的LD_(50)为603.3 mg/kg;ig对大鼠的LD_(50)为3 188.7 mg/kg。欧前胡素单次ig对小鼠神经系统无明显影响;单次po对犬心血管系统指标和呼吸系统指标无明显影响。结论欧前胡素安全范围较大,毒性较容易控制,且对正常动物(包括小鼠、大鼠和犬)的降压作用不显著,因此具有较大的临床应用可能性。

Objective To determine the acute toxicity of imperatorin on rats and mice, and the influence of imperatorin on the nervous system of mice and the cardiovascular and respiratory systems of beagle dogs. Methods intraperitoneal injection （ip） and intragastric administration （ig） were performed to mice and ig to rats to determine the acute toxicity of imperatorin. In safety pharmacology experiments, ip of imperatorin was performed to mice in single doses of 50, 100, and 200 mg/kg to observe its influence on the nervous system of mice （ including locomotor activity, pole climbing ability, and collaborative hyposis experiment of threshold dose of sodium pentobarbital, etc. ）. Oral administration （po） of imperatorin was also performed in single doses of 25, 50, 100 mg/kg to beagle dogs to observe its influence on the cardiovascular and respiratory systems of dogs （ including ECG, blood pressure, heart rate, and breathing indexes, etc. ）. Results The LD50 of imperatorin to mice is 988.5 mg/kg by ig and 603.3 mg/kg by ip, and to rats is 3188.7 mg/kg by ig. No significant effects on the nervous system of mice were observed by single ip of imperatorin. And no significant effects on the cardiovascular and respiratory systems of beagle dogs were observed by single po of imperatorin. Conclusion Imperatorin had a wide range of safety application, and its toxicity was relatively easy to control. The antihypertensive effects of imperatorin on normal animals （including mice, rats and dogs） were not significant, therefore it had a great possibility in clinical application.