附子甘草药对组分配伍减毒机理研究

【作者】 胡一冰；

【导师】 彭成；

【作者基本信息】 成都中医药大学 ， 方剂学， 2005， 博士

【摘要】 目的:研究附子、甘草各组分的毒性,探讨附子甘草药对组分配伍减毒的物质基础及作用机理。 方法:用动物急性毒性实验观察附子酯性生物碱,附子水溶性生物碱、附子多糖、甘草黄酮、甘草皂苷各组分的毒性。应用附子酯性生物碱的心脏毒性,建立新的心律失常动物模型,并观察附子甘草各组分对其造成心律失常动物模型的影响。采用MTT法、血清药理法、姬姆萨染色法、电镜方法、细胞酶学方法,观察附子甘草各组分对附子酯性生物碱致体外原代培养心肌细胞毒性的解毒作用,揭示其作用机理。 结果:附子水溶性生物碱、附子酯性生物碱有毒,以附子酯性生物碱毒性最大,附子多糖、甘草黄酮、甘草皂苷均未见明显毒性。附子水溶性生物碱、甘草皂苷对附子酯性生物碱所致动物心律失常模型有拮抗作用,附子多糖、甘草黄酮未见有拮抗作用。附子水溶性生物碱与附子酯性生物碱配伍后可明显升高培养心肌细胞活力,减少培养心肌细胞凋亡,维护正常细胞胞膜、线粒体、粗面内质网、核糖体、肌丝的基本完整性,升高Na~+-K~+-APT酶的活性。附子多糖,甘草黄酮、甘草皂苷分别与附子酯性生物碱配伍后未见升高培养心肌细胞活力和减少培养心肌细胞凋亡,甘草皂苷与附予酯性生物碱配伍后,未见对附子酯性生物碱造成心肌细胞Na~+-K~+-APT酶活性降低有升高作用,对心肌亚细胞结构毒性也未见有减轻作用。 结论:附子酯性生物碱毒性最大;附子酯性生物碱对心脏毒性表现为可以导致动物心律失常:附子水溶性生物碱、甘草皂苷具有抗心律失常作用,附子多糖,甘草黄酮不具有抗心律失常作用。附子水溶性生物碱可能通过升高心肌细胞活力,减少心肌细胞凋亡,升高Na~+-K~+-APT酶活性来维护正常细胞胞膜、线粒体、粗面内质网、核糖体、肌丝的基本完整性,维持正常能量代谢,来对抗附子酯性生物碱对心肌细胞的毒性作用。更多还原

【Abstract】 Objective: Researching the component parts toxicity of acontum fischeri mankshood and liquorice root ,and discussing the hylic base and mechanism of reductive toxicity after compatibility between them.Methods: To observe component parts toxicity of acontum fischeri mankshood fatsoluble alkaloid, acontum fischeri mankshood water-solubility alkaloid, acontum fischeri mankshood amylose, liquorice flavone, liquorice saponin by acute virulent animal experiment. To establish the rats arrhuthmic animal mldel with the biggest toxicity component part, acontum fischeri mankshood fatsoluble alkaloid,and observe the function to this arrhuthmic animal mldel with the component parts of acontum fischeri mankshood and liquorice root. In order to observe component parts alexipharmic effect and mechanism of acontum fischeri mankshood and liquorice root to acontum fischeri mankshood fatsoluble alkaloid toxicity on exosomatic germinal incubatory myocardial cell.With the methods of MTT, serum pharmacology, Giemsa staining ,electron microscope,cell enzymology.Results: The poisonous component parts are acontum fischeri mankshood water-solubility alkaloid and acontum fischeri mankshood fatsoluble alkaloid,The biggest poisonous component part is acontum fischeri mankshood fatsoluble alkaloid.The acontum fischeri mankshood amylose, liquorice flavone, liquorice saponin are no toxicity. The antiarrhythmic component parts are acontum fischeri mankshood water-solubility alkaloid and liquorice saponin . Acontum fischeri mankshood amylose and liquorice flavone have no antiarrhythmic function. The compatibility of acontum fischeri mankshood water-solubility alkaloid and acontum fischeri mankshood fatsoluble alkaloid can increase myocardial cell vitality,debase cultural myocardial cell apoptosis, vindicate the integrality of cytolemma, chondriosome , rough endoplasmic reticulum , ribosome , myofilament, raise enzymatic vigor,but acontum fischeri mankshood amylose, liquorice flavone, liquorice saponin can’t.Conclusions: The poisonous component parts are acontum fischeri mankshood water-solubility alkaloid and acontum fischeri mankshood fatsoluble alkaloid,The biggest poisonous component part is acontum fischeri mankshood fatsoluble alkaloid,which result in animal arrhythmia.The antiarrhythmic component parts are acontum fischeri mankshood water-solubility alkaloid and liquorice saponin .Acontum fischeri mankshood amylose and liquorice flavone have no antiarrhythmic function. Acontum fischeri mankshood amylose can antagonize acontum fischeri mankshood fatsoluble alkaloid toxicity on myocardial cell.更多还原