湖北医药学院学报2025,Vol.44Issue(6):672-680,9.DOI:10.13819/j.issn.2096-708X.2025.06.004
褪黑素通过调节L型钙电流改善睡眠剥夺大鼠房颤易感性
Melatonin Ameliorates the Susceptibility to Rtrial Fibrillation in Sleep-Deprived Rats via Modulation of L-Type Calcium Current
摘要
Abstract
Objective To examine the impact of melatonin on the susceptibility to atrial fibrillation(AF)in sleep-deprived(SD)rats and elucidate the underlying mechanisms from both electrophysiological and ion channel perspectives.Methods Thirty male Sprague-Dawley rats were randomly allocated to three groups:a control group,a sleep deprivation group(SD group),and a melatonin intervention group(SD+MLT group).A sleep deprivation model was established utilizing the modified multiple platform method.The SD+MLT group received intraperitoneal injections of melatonin at a dosage of 20 mg/kg/day for three consecutive days prior to the induction of sleep deprivation.Programmed electrical stimulation was em-ployed to evaluate the atrial effective refractory period(AERP)and AF inducibility.Microelectrode array(MEA)technolo-gy was used to assess left atrial conduction velocity and heterogeneity.Additionally,patch-clamp techniques were employed to record action potential(AP)characteristics and L-type calcium current(ICa,L)in primary atrial myocytes.Results In comparison to the control group,the SD group had a higher AF inducibility rate(7/10 vs.1/10,P<0.05),reduced AERP(50.00±6.67 ms vs.75.00±7.07 ms,P<0.05),decreased conduction velocity(26.45±4.04 cm/s vs.91.72±7.94 cm/s,P<0.05),and elevated heterogeneity index(5.03±0.45 vs.1.97±0.36,P<0.05).Additionally,SD was associated with pro-longed action potential duration(APD90,APD50,APD30),diminished ICa,L density,and a rightward shift in the steady-state inactivation curve(all P<0.05).Intervention with melatonin significantly ameliorated these electrophysiological re-modeling parameters,resulting in improved AF inducibility(3/10),AERP(68.00±6.32 ms),conduction velocity(46.15±7.07 cm/s),and heterogeneity index(3.05±0.41),while partially restoring ICa,L density and inactivation kinetics.Con-clusion Sleep deprivation causes changes in atrial electrical activity,raising the risk of AF.Melatonin helps counteract these changes and reduces AF risk by enhancing conduction heterogeneity,restoring AERP,and modulating ICa,L function.This study confirms that melatonin can be a preventive and therapeutic option for AF related to sleep deprivation.关键词
褪黑素/睡眠剥夺/心房颤动/L型钙电流Key words
Melatonin/Sleep deprivation/Atrial fibrillation/L-type calcium current引用本文复制引用
SHEN Jun,CUI Zi-heng,YAO Ling-ling,ZHANG You-en,Tang Bao-peng,WANG Jia-ning..褪黑素通过调节L型钙电流改善睡眠剥夺大鼠房颤易感性[J].湖北医药学院学报,2025,44(6):672-680,9.基金项目
国家自然科学基金资助项目(82370326,81270221) (82370326,81270221)
湖北省教育厅中青年人才项目(Q20212102) (Q20212102)
湖北省卫健委面上项目(WJ2025M027) (WJ2025M027)
湖北省教育厅引导性项目(B2024432) (B2024432)