Su Liping, Liu Li, Ji Min, Hu Xiayun, Liang Min, Lu Ziyang, Wang Zhiguo, Guan Yaling, Xiao Jinling, Zhuang Mengjie, Zhu Sensen, Yang Long, Pu Hongwei
Department of Pathology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang, PR China.
School of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang, PR China.
Open Med (Wars). 2023 Jul 31;18(1):20230765. doi: 10.1515/med-2023-0765. eCollection 2023.
Heroin can cause damage to many human organs, possibly leading to different types of arrhythmias and abnormal electrophysiological function of the heart muscle and the steady state of calcium-ion channels. We explored cardiomyocytes treated with heroin and the effect on calcium-ion channels. Transcriptomics and metabolomics were used to screen for differential genes and metabolite alterations after heroin administration to jointly analyze the effect of heroin on calcium channels in cardiomyocytes. Cardiomyocytes from primary neonatal rats were cultured and were treated with different concentrations of heroin to observe the changes in morphology and spontaneous beat frequency and rhythm by a patch clamp technique. Transcriptomic studies selected a total of 1,432 differentially expressed genes, 941 upregulated and 491 downregulated genes in rat cardiomyocytes from the control and drug intervention groups. Gene Ontology functional enrichment showed that 1,432 differential genes selected by the two groups were mainly involved in the regulation of the multicellular organismal process, response to external stimulus, myofibril, inflammatory response, muscle system process, cardiac muscle contraction, etc. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that these genes were mainly concentrated in cardiac muscle contraction, osteoclast differentiation, adrenergic signaling in cardiomyocytes, dilated cardiomyopathy, hypertrophic cardiomyopathy, and other important pathways. Metabolomic testing further suggested that cardiomyocyte metabolism was severely affected after heroin intervention. After the treatment with heroin, the L-type calcium channel current - curve was up-shifted, the peak value was significantly lower than that of the control group, action potential duration 90 was significantly increased in the action potential, resting potential negative value was lowered, and action potential amplitude was significantly decreased in cardiomyocytes. In this study, heroin could cause morphological changes in primary cardiomyocytes of neonatal rats and electrophysiological function. Heroin can cause myocardial contraction and calcium channel abnormalities, damage the myocardium, and change the action potential and L-type calcium channel.
海洛因可对人体多个器官造成损害，可能导致不同类型的心律失常以及心肌电生理功能异常和钙离子通道稳态失衡。我们研究了海洛因处理的心肌细胞及其对钙离子通道的影响。采用转录组学和代谢组学方法筛选海洛因给药后差异基因和代谢物变化，以联合分析海洛因对心肌细胞钙离子通道的作用。培养原代新生大鼠心肌细胞，用不同浓度海洛因处理，采用膜片钳技术观察细胞形态、自发搏动频率和节律的变化。转录组学研究共筛选出1432个差异表达基因，对照组和药物干预组大鼠心肌细胞中上调基因941个，下调基因491个。基因本体功能富集分析表明，两组筛选出的1432个差异基因主要参与多细胞生物体过程调控、对外界刺激的反应、肌原纤维、炎症反应、肌肉系统过程、心肌收缩等。京都基因与基因组百科全书通路富集分析表明，这些基因主要集中在心肌收缩、破骨细胞分化、心肌细胞肾上腺素能信号传导、扩张型心肌病、肥厚型心肌病等重要通路。代谢组学检测进一步提示，海洛因干预后心肌细胞代谢受到严重影响。海洛因处理后，心肌细胞L型钙通道电流曲线向上移位，峰值显著低于对照组，动作电位时程90在动作电位中显著增加，静息电位负值降低，动作电位幅度显著减小。本研究表明，海洛因可引起新生大鼠原代心肌细胞形态改变和电生理功能变化。海洛因可导致心肌收缩和钙通道异常，损害心肌，改变动作电位和L型钙通道。
