葡萄内酯的安全性药理学研究  

Study on Safety Pharmacology of Auraptene

作　　者：叶喜德[1,2] 黄兆胜[2] 陈海芳[1] 袁金斌[1] 黄丽萍[1] 余日跃[1] 杨武亮[1] 

机构地区：[1]江西中医学院现代中药制剂教育部重点实验室,南昌330004 [2]广州中医药大学,广州510006

出　　处：《中药新药与临床药理》2012年第5期522-526,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金资助项目(30660230);"重大新药创制"科技重大专项"十一五"计划资助(2009ZX09103-350)

摘　　要：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 investigate the influences of auraptene on mice spontaneous activity, hypnotic effect in pentobarbital-sodium-anesthetized mice and on eleetrocardiogram（ECG）, blood pressure, and respiration in anesthetized beagles. Methods Oral administration of auraptene in the doses of 2.055, 20.55 and 205.5 mg.kg-1 was given to the normal mice and the anesthetized mice and beagle dogs by intraperitoneal injection of subthreshold dosage of pentobarbital sodium. After administration, we observed mice spontaneous activity, hypnotic effect in pentobarhital-sodiurn-anesthetized mice and on ECG, blood pressure, and respiration in anesthetized beagles. Results Auraptene had no effect on mice spontaneous activity, and had no synergistic action on hypnotic effect induced by subthreshold dosage of pentobarhital sodium. Low-, medium- and high-dose auraptene had no effect on blood pressure of anesthetized beagle dogs, and had no effect on P-R, Q wave, T wave amplitude, or ST segment of ECG as well as respiratory frequency and depth in anesthetized dogs bfore and after administration, the inter-group differences being signif- icant（P 〉 0.05）. Conclusion The results of safety pharmacological study showed that 205.5 mg.kg-1, the high dose of auraptene in mice, is 20 times as much as clinical adult dosage. The high doses of auraptene for anesthetized dogs are 102.80 mg/kg or less than 102.80 rag/kg . Single-dose auraptene has on effect on spontaneous activity in mice, hypnotic effect in pentobarbital-sodium-anesthetized mice or on ECG, blood pressure, and respiration in anesthetized beagles, indicating that auraptene being safe. The result will supply important pharmacological experimental data for further research of developing auraptene into a new drug.

关 键 词：葡萄内酯 安全性药理 小鼠自主活动 麻醉犬 

分 类 号：R285.5[医药卫生—中药学]