乌头类有毒中药毒性成分对心肌细胞膜受体作用机制的研究

【作者】 王艳美；

【导师】 彭成；

【作者基本信息】 成都中医药大学 ， 方剂学， 2007， 硕士

【摘要】 目的:研究乌头类有毒中药毒性成分乌头碱、新乌头碱和次乌头碱对心肌细胞膜受体作用的机制。方法:本实验采用放射配基结合分析法(radioligand bind assay,RBA)研究乌头碱、新乌头碱和次乌头碱对心肌细胞肾上腺素能受体不同亚型的影响;用放射受体分析法(radioreceptor assay,RAA)研究乌头碱、新乌头碱和次乌头碱对心肌细胞IP3和cAMP/cGMP比值的影响,从而揭示乌头碱、新乌头碱及次乌头碱对心肌细胞肾上腺素能受体不同亚型及乌头碱对心肌细胞信号转导途径的影响。结果:乌头碱对心肌细胞作用1分钟时,可引起心肌细胞a1—AR数量上调,但对a1—AR的亲和力无影响;对心肌细胞β1—AR、β2—AR的亲和力和受体数量均无影响。新乌头碱和次乌头碱对心肌细胞作用1分钟时,a1—AR、β1—AR、β2—AR的亲和力和受体数量均无影响。乌头碱、新乌头碱及次乌头碱在不同时间点作用于心肌细胞后,给药组IP3和cAMP/cGMP的比值与正常组相比均升高。结论:1.乌头碱对心肌细胞作用1分钟时,对a1—AR有影响,对β—AR无影响;新乌头碱及次乌头碱对心肌细胞作用1分钟时,a1-和β—AR均无变化。2.乌头碱、新乌头碱及次乌头碱对心肌细胞内IP3和cAMP/cGMP均有影响。3.乌头碱对心肌细胞的损伤可能是通过多信号转导途径实现的。更多还原

【Abstract】 Objiective:To research the mechanisms of the venenons constituent of the Aconitum—aconitine、mesaconitine、hypaconitine on the membrane receptor of myocardial cell.Methods:Researching the influence that aconitine mesaconitine and hypaconitine act on the adrenoceptor subtype of the myocardial cell by RBA. Researching the effect that aonitine masaconitine and hypaconitine act on the IP3 and cAMP/cGMP of the myocardial cell by RAA.On the basis of these experiment,it is revealed that effect that aconitine mesaconitine and hypaconitine act on the adrenoceptor subtype and signal transduction pathway of the myocardial cell.Results:Aconitine acting on the myocardial cell produce up-regulation of a1-adrenergic receptors,but has no effect on the affinity of a1-adrenergic receptors. Aconitine has no effect on the affinity and quantity ofβ-adrenergic receptors of the myocardial cell.Mesaconitine and hypaconitine have no influence on the affinity and quantity of a1 andβ-adrenergic receptors.After aconitine mesaconitine and hypaconitien acting on the myocardial cell in different time,the IP3 and the ratio of the cAMP/cGMP of MAT increased than normal group.Conclusion:1.Aconitine has no effect on a1-adrenergic receptors,but no effect on the affinity and quantity ofβ-adrenergic receptors of the myocardial cell.Mesaconitine and hypaconitine have no influence on the affinity and quantity of a1 andβ-adrenergic receptors.2.After aconitine mesaconitine and hypaconitien acting on the myocardial cell,the IP3 and the ratio of the cAMP/cGMP of MAT increased3.The toxic effect of aconitine action on the myocardial cell may have multiple signal transduction pathway.更多还原