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新型环糊精衍生物HP_n-SBE_m-β-CD动物血管给药的生物效应评价

Biological effect of noveal cyclodextrin derivative HP_n-SBE_m-β-CD intravenous administration on animals

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【作者】 王晖陈乘周成梁余书勤

【Author】 WANG Hui,CHEN Cheng,ZHOU Cheng-liang,YU Shu-qin( College of Life Science,Nanjing Normal University, Jiangsu Key Laboratory of Supramolecular Medicinal Materials and Applications,Nanjing 210046,China)

【机构】 南京师范大学生命科学学院江苏省医药超分子材料及应用重点实验室

【摘要】 目的:研究羟丙基-磺丁基-β-环糊精(HPn-SBEm-β-CD)对动物红细胞的溶血和形态改变及对动物神经、呼吸及心血管系统的影响。方法:采用紫外分光光度法检测11种HPn-SBEm-β-CD对红细胞的溶血作用;扫描电镜观察HP3-SBE2-β-CD红细胞形态的变化;给小鼠分别静脉注射80、160及320 mg.kg-1的HP4-SBE3-β-CD后对小鼠一般行为和自主活动次数等进行观察;将Beagle犬麻醉后静脉注射40、80及160 mg.kg-1的HP4-SBE3-β-CD,检测其对呼吸频率、幅度及心电、心率和血压的影响。结果:11种HPn-SBEm-β-CD溶血性均明显低于β-CD,多数化合物溶血性显著低于HP-β-CD,其中HP2-SBE3-β-CD、HP1-SBE4-β-CD、HP3-SBE6-β-CD等化合物的溶血性低于SBE7-β-CD。10 mmol.L-1HP3-SBE2-β-CD对红细胞形态无影响,而2.5 mmol.L-1 M-β-CD能明显改变红细胞的形态;给定剂量条件下HP4-SBE3-β-CD不改变小鼠的一般行为和自主活动次数;对麻醉犬的呼吸频率、幅度及心电、心率和血压均无明显影响(P>0.05)。结论:HPn-SBEm-β-CD溶血性小,对小鼠神经精神系统无影响,对麻醉犬的呼吸系统及心血管系统均无明显的影响。

【Abstract】 Objective: To investigate the effects of hydroxypropyl-sulfobutyl ether-β-cyclodextrins(HPn-SBEm-β-CD)on hemolysis and morphological changes of red blood cells(RBC) and on nervous system,respiratory system and cardiovascular system in animals. Methods: RBC were treated by 11 different degrees of substitution of HPn-SBEm-β-CD and hemolysis was detected by UV.Scanning electron microscopy(SEM) was used to observe the effect of HP3-SBE2-β-CD on morphological changes of RBC.Experimental mouse were given 80,160,and 320 mg·kg-1 HP4-SBE3-β-CD by intravenous.Different physical parameters such as common behavior,times of free activities were observed.Beagle dogs were given 40,80,and 160 mg·kg-1 HP4-SBE3-β-CD by intravenous after anaethesia and the respiratory frequency,and extent as well as ECG,blood pressure heart rate and were detected.Results: The hemolytic activity of HPn-SBEm-β-CDwas all less than β-CD.The hemolytic activity of most compounds were less than the HP-β-CD,some of the them such as HP2-SBE3-β-CD、HP1-SBE4-β-CD and HP3-SBE6-β-CD were also less than the SBE7-β-CD.10 mmol·L-1 HP3-SBE2-β-CD had no effect on morphological changes of RBC,but 2.5 mmol·L-1 M-β-CD had effect on it obviously.HP4-SBE3-β-CD of 80,160,and 320 mg·kg-1 had no effect on behavior and times of free activities.HP4-SBE3-β-CD had no obvious effect on the respiratory frequency and extent,ECG,heart rate and blood pressure.Conclusion: HPn-SBEm-β-CD with low hemolysis has no effect on the nervous system of mouse,and also has no effect on respiratory system and cardiovascular system of anesthetical dogs.

【基金】 国家科技重大专项:重大新药创制课题(2009ZX09103-044)
  • 【文献出处】 东南大学学报(医学版) ,Journal of Southeast University(Medical Science Edition) , 编辑部邮箱 ,2011年02期
  • 【分类号】R965
  • 【下载频次】115
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