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目的观察葡萄内酯(auraptene)对实验动物小鼠自主活动、小鼠戊巴比妥钠催眠作用和对麻醉比格犬心电图、血压及呼吸的影响。方法采用小鼠灌药、小鼠腹腔注射阈下剂量戊巴比妥钠和麻醉犬给药等方法,分别观察低、中、高3个剂量的葡萄内酯(2.055,20.55,205.5 mg.kg-1)对小鼠自主活动、小鼠戊巴比妥钠催眠作用和对犬心电图、血压、呼吸等指标的影响。结果葡萄内酯对小鼠自主活动均无明显影响,与小鼠戊巴妥钠阈下催眠剂量无协同作用;低、中、高剂量葡萄内酯对麻醉犬血压无明显影响,对给药前后犬心电图P-R、ST波、Q波、T波波幅、ST段和呼吸频率、呼吸深度也无明显影响,各组间比较,差异无统计学意义(P>0.05)。结论安全性药理学研究表明,实验用药小鼠高剂量205.5 mg.kg-1为临床成人拟用药剂量的20倍,犬用药高剂量为102.80 mg.kg-1及以下剂量,葡萄内酯单次给药对小鼠自主、小鼠戊巴比妥钠催眠作用和麻醉犬心电图、血压、及呼吸等无明显影响,提示葡萄内酯具有较高的安全性。
Objective To observe the effect of auraptene on the autonomic activity of mice, the hypnotic effect of pentobarbital sodium and the electrocardiogram, blood pressure and respiration of anesthetized beagle dogs. Methods Mice were drenched into mice, mice were injected intraperitoneally with subthreshold dose of sodium pentobarbital and anesthetized dogs. The effects of low, medium and high dosage of three doses (2.055, 20.55, 205.5 mg.kg -1) on mouse autonomic activity, mice hypnotic effect of pentobarbital sodium and ECG, blood pressure, respiration and other indicators of dogs. Results There was no significant effect of grape lactone on spontaneous activity in mice, but no synergistic effect with the subthreshold hypnotic dose of pentobarbital in mice. Low, middle and high dose of grape lactone had no significant effect on blood pressure of anesthetized dogs. There were no significant differences in the PR, ST wave, Q wave, T wave amplitude, ST segment, respiratory rate and respiratory depth in dogs. There was no significant difference between the groups (P> 0.05). Conclusions The study of safety pharmacology shows that the high dose of 205.5 mg.kg-1 in experimental mice is 20 times higher than that of clinical adult, and the high dose of canine is 102.80 mg.kg-1 and below, Administration had no significant effect on autonomic mice, mice hypnotic effect of pentobarbital sodium, ECG, blood pressure and respiration of anesthetized dogs, suggesting that the lactone has high safety.