红花黄素对氧自由基所致的心肌细胞电生理异常的保护作用(英文)

Effect of safflower yellow pigment on abnormal electrophysiology of cardiac myocytes induced by oxygen-derived free radical

背景:氧自由基诱导的功能异常可能使心脏、肝脏、肾脏及脑等组织缺血性疾病的主要致病因素,对损伤有保护作用的药物研究成为当前的热点。目的:研究红花黄素(Saffloweryellowpigment,SYP)对氧自由基引起的豚鼠单个心室肌细胞损伤的保护作用。设计:非随机对照的实验研究。地点、材料和干预:本实验在哈尔滨医科大学药学院药理教研室完成。实验选用豚鼠30只,性别不限。以处置前单个心室肌细胞为正常对照,预先应用红花黄素(3.3μg/L)后,给予单个豚鼠心室肌细胞外源性氧自由基(1mmol/L的H2O2)。主要观察指标:采用全细胞膜片钳技术,观察单个豚鼠心室肌细胞动作电位时程(actionpotentialdurationAPD)和L-型钙电流、内向整流钾电流。结果:1mmol/L的H2O2导致豚鼠心室肌细胞损伤,表现为动作电位时程缩短,APD50和APD90分别由正常对照组的(331.2±31.9)ms和(380.8±28.2)ms缩短至(169.5±76.0)ms和(238.4±21.3)ms(n=8,t=3.834,P<0.01),红花黄素(3.3μg/L)能明显改善H2O2诱发的动作电位时程缩短;同时氧自由基H2O2抑制L-型钙电流,+10mV时,L-型钙电流峰值由对照的(-1023.45±74.34)pA减少到(-275.21±38.67)pA(n=6,P<0.001);H2O2(1mmol/L)也明显抑制内向整流钾电流(IK1),指令电位为-120mV时,IK1由对照组的(-2133.

BACKGROUND:Dysfunction induced by free radicals is the major cause of ischemic diseases of the heart,bowel,liver,kidney,and brain.It is a hot topic to develop drugs which can prevent cells from damages caused by free radicals. OBJECTIVE:To study the protective effect of safflower yellow pigment(SYP) on t he electrophysiological abnormality induced by oxygen derived free radical in si ngle guinea pig ventricular myocytes. DESIGN:Non randomized case control study. SETTINGS, PARTICIPANTS and INTERVENTIONS:This study was completed in Departmen t of Pharmacology of Harbin Medical University.A total of 30 guinea pigs were se lected without considering gender.The single ventricle myocyte before interventi on was used as normal control.Exogenous oxygen derived free radicals(1 mmol/L o f H2O2) were given to single ventricle myocyte of guinea pig when SYP(3.3 μg/L) was given in advance. MAIN OUTCOME MEASURE:Whole cell patch clamp techniques were used to record ac tion potential duration (APD), L type calcium current(ICa) and inward rectifier potassium current(Ik1). RESULTS:H2O2(1 mmol/L) led to the damage of ventricle myocytes of Guinea pig w hich was presented by decrease of action potential duration.The APD50 and APD90 were shortened from (331.2±31.9) ms and(380.8 ±28.2) ms to(169.5±76.0) ms and (238.4±21.3) ms(n=8,t =3.834,P< 0.01)respectively.Pretreatment with SYP(3.3 μg/L ) could markedly attenuate the injury effect of H2O2 on APD; H2O2 signific antly inhibited L type calcium current (ICa)from(-1 023.45±74.34) pA to(-275 .21±38.67) pA(n=6,P< 0.001) at the test potential 10 mV. H2O2 also inhibited i nward rectifier potassium current of normal group from (-2 133.5±570.4) pA to( -567.0±218.0) pA at the test potential of -120 mV.Although the inhibitory eff ects on L type ICa of ventricle myocytes for ten minutes,which caused by exogen ous oxygen derived free redicals could be improved,the effect of H2O2 on Ik1 co uld not be changed. CONCLUSION:SYP can antagonise the damage induced by free radical.It suggests t hat free radical can be cleared away by SYP.This study provides the mechanical b asis for the treatment of ischemic heart disease and invention of rehabilitation .