Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats
作者单位：Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal MedicineMinistry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences & Peking Union Medical College Academy of Chinese Medical Sciences of Jilin Province
会议名称：《中国微循环学会2014年全国学术会议》
会议日期：2014年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：Aconitine Apoptosis Arrhythmia Heart Calcium overload Cardiotoxicity
摘 要：Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum *** evidence indicates that voltage-dependent Na+channels have pivotal roles in the cardiotoxicity of ***,no reports are available on the role of Ca2+in aconitine *** this study,we explored the importance of pathological Ca2+signaling in aconitine poisoning in vitro and in *** found that Ca2+overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving *** investigate effects of aconitine on myocardial injury,we performed cytotoxicity assay in neonatal rat ventricular myocytes（NRVMs）,as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in *** results showed that aconitine resulted in myocardial injury and reduced NRVMs viability *** confirm the pro-apoptotic effects,we performed flow cytometric detection,cardiac histology,transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling *** results showed that aconitine stimulated apoptosis *** expression analysis of Ca2+handling proteins demonstrated that aconitine promoted Ca2+overload through the expression regulation of Ca2+handling *** expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated,and anti-apoptotic protein BCL-2expression was ***,increased phosphorylation of MAPK family members,especially the P-P38/P38 ratio was found in cardiac ***,our results suggest that aconitine significantly aggravates Ca2+overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38mitogen-activated protein kinase.