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作 者:庞晶[1] 刘尚裕[1] 张伟新[1] 李国庆[1] 杨信怡[1] 李聪然[1] 游雪甫[1]
机构地区:[1]中国医学科学院北京协和医学院医药生物技术研究所药理室,北京100050
出 处:《中国医药生物技术》2015年第1期31-38,共8页Chinese Medicinal Biotechnology
基 金:"十二五"国家科技重大专项(2008ZX09305-001;2012ZX0 9301002-001;2012ZX09301002-005)
摘 要:目的研究丹参抗HIV有效部位(DS-MEF)对小鼠精神神经系统的影响、对麻醉犬心血管系统和呼吸系统的影响以及长期给药对大鼠产生的毒性反应,为DS-MEF的进一步研究和应用提供依据。方法 DS-MEF 2000、4000、8000 mg/kg对小鼠灌胃给药一次后,观察其对小鼠自主活动、协调平衡运动以及戊巴比妥钠阈下催眠作用的影响;DS-MEF 500、1000、2000 mg/kg对犬灌胃给药一次后,考察240 min内其对犬血压、心率、心电图和呼吸系统的影响;DS-MEF 2000、4000、8000 mg/kg对大鼠连续灌胃给药12周,末次给药24 h和停药3周后,每组取半数动物(雌雄各半)进行体重、血液学、血液生化、尿液、脏器系数及病理组织学变化等检查。结果 DS-MEF对小鼠精神神经系统未见明显影响;对犬血压、心率和心电图各指标以及呼吸频率和呼吸深度未见明显影响;长期给药后,大鼠外观体征、一般活动等未见异常,体重变化和饲料消耗量与对照组比较无显著差异,动物心、肝、脾、肺、肾等主要脏器组织病理学检查未见药物引起的异常改变。结论本实验条件下,未观察到丹参有效部位对小鼠精神神经系统、对犬的心血管系统和呼吸系统的显著影响,且在长期毒性研究中,未见其对大鼠产生显著的毒性反应。Objective The effects of anti-HIV effective fraction of Salvia (DS-MEF) on mouse’s nervous system and canine cardiovascular and respiration systems, as well as its long-term toxicity in rats were investigated so as to provide evidence for further research and its application. Methods The effects of the effective fraction of Salvia on the locomotor activity, motor balance and coordination, and nembutal subthreshold hypnosis of mice were evaluated after a single oral dose of 2000, 4000 and 8000 mg/kg test article. The effects of a single oral administration of 500, 1000 and 2000 mg/kg DS-MEF on dogs were investigated within 240 minutes for its impact on the blood pressure, heart rate, ECG and respiratory system. After 12-week repeated doses of 2000, 4000 and 8000 mg/kg, half animals of each group (half male and half female) were sacrificed at 24 h and 3 weeks post last dose for detection of body weight, hematology, blood biochemistry, urine, organ coefficient, and histopathological changes, respectively. Results The anti-HIV effective fraction of Salvia exhibited no effect on the nervous system of mice. No significant impact on blood pressure, heart rate, ECG, and respiratory depth and rate of dogs was observed. After long-term administration to rats, no abnormality was observed in the appearance characteristics and general activities, no significant difference in body weight and food consumption was found between the dosing groups and control group, and no abnormal change was detected in heart, liver, spleen, lung, kidney, and other major organs in the histopathological examinations. Conclusion The anti-HIV effective fraction of Salvia did not show significant impact on the nervous system of mice, cardiovascular and respiratory system of dogs. No significant DS-MEF related toxicity effect was observed in the long-term toxicity research in rats as well.
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