蛇床子素对阿霉素心脏毒性的保护作用及机制研究

Osthol Adriamycin Cardiac Toxicity and Mechanism of The Protective Effect of Study

目的:研究蛇床子素(Osthol,Ost.)对阿霉素(Adriamycin,ADR.)引起的心脏毒性的保护作用,并探讨其机制。方法:用SD大鼠腹腔注射ADR的方法复制ADR心脏毒性模型。用透射电镜观察心肌细胞超微结构,激光共聚焦显微镜测定心肌细胞Ca2+浓度,采用酶促反应定磷比色法测定心肌细胞膜Na+-K+-ATP酶活性。结果:ADR累积用量20mg.kg-1可致大鼠心肌纤维断裂,线粒体肿胀,游离Ca2+浓度升高,细胞膜Na+-K+-ATP酶活性降低。加用Ost后可减轻ADR对大鼠心肌超微结构的损伤,降低心肌细胞内游离Ca2+浓度,升高心肌细胞膜Na+-K+-ATP酶的活性。结论:Ost对ADR引起的心脏毒性有保护作用,其机制可能与其激活心肌细胞膜Na+-K+-ATP酶的活性,加速细胞内外Na+/Ca2+交换,降低细胞内Ca2+浓度、阻止Ca2+超载有关。

Objective： Study of adriamycin osthol cardiac toxicity caused by the protective effect and its mechanism.Methods： SD rats by intraperitoneal injection of doxorubicin way to copy the model of adriamycin cardiotoxicity.Observed by transmission electron microscopy the ultrastructure of myocardial cells,determination of laser scanning confocal microscope myocyte Ca2 ＋ concentration,enzymatic reaction using colorimetric determination of phosphorus determined myocardial membrane Na ＋-K ＋-ATP activity.Results： ADR may be caused by the cumulative amount of 20mg/kg rat cardiac fiber fracture,Mitochondrial swelling,Free calcium concentration increased,Membrane Na ＋-K ＋--ATP activity decreased.Osthol reduce adriamycin on ultrastructure of rat myocardial injury,Reduce the myocardial concentration of intracellular free calcium,increased myocardial membrane Na ＋-K ＋-ATP enzyme activity.Conclusion： Osthol adriamycin-induced cardiac toxicity has a protective effect on,the mechanism may be related to active the Na ＋-K ＋-ATP,increase the exchange of Na ＋ /Ca2 ＋,then degrade the concentration of Ca2 ＋,and arrest calcium overload.