缬草提取物对慢性心力衰竭室性心律失常兔电生理指标的影响∗

摘要

Objective:To investigate effects of valeriana officinalis L extract (VOL)on correlated electrophys-iological parameters of ventricular arrhythmias induced by congestive heart failure (CHF)in rabbits.Method:The male New Zealand rabbits (n=30)were divide into control,CHF and CHF+VOL (VOL)groups.The CHF mod-els were induced by injection isoproterenol (0.3mg/Kg/d for 3 weeks),and control rabbits were injected 0.9%NaCl with same ways.The VOL group rabbits were injected 50mg/L VOL.The main cardioelectrophysiological pa-rameters such as RMP,APA,Maxdv/dt and APD10-90 ,as well as basic cycle length (BCL),rate and time of induced arrhythmias by recording monophasic action potential (MAP)with Burst-pacing in rabbits in vivo with 50mg/L VOL administration.The L-type calcium current (ICa-L )was recorded via whole-cell patch clamp technique in enzy-matically dissociated single rabbit ventricular myocytes.Results:Compared with control group,RMP,APA and Maxdv/dt were significantly lowered,as well as APD10-90 were notably lingered in CHF rabbit (P of all <0.01,re-spectively).Compared with CHF group,VOL could significantlyincrease RMP,APA and Vmax ,as well shorten APD10-90 inVOL group in vivo (P of all <0.01,respectively).Compared with control group,BCL and persistence time inducing ventricular arrhythmias were significantly lengthened,and occurrence of ventricular arrhythmias were obviously increased in CHF group (P of all <0.01,respectively).However,VOL could obviously shorten BCL and persistence time of ventricular arrhythmias,and decrease rate of inducibility of ventricular arrhythmias with burst-pacing in VOL group in vivo (P of all <0.01,respectively).VOL could markedly increase the current densi-ty of ICa-L ,and alter down of current-voltage (I-V)relationship curve in different command potential in CHF ventric-ular myocytes.When command potential was +20mV,the current densities of ICa-L were significantly increased from (7.14±0.33)pA/pF in CHF group to (10.86±0.50)pA/pF in VOL group(P<0.01)with VOL administration. Conclusion:VOL could significantly decrease the vulnerability and susceptibility of ventricular arrhythmias induced by CHF,which was contributed to anti-ventricular arrhythmias induced by CHF.It is suggested that the mecha-nisms might attribute to that VOL could markedly increase ICa-L in CHF rabbits.%目的：观察缬草提取物(VOL)对慢性心力衰竭(CHF)致室性心律失常兔电生理指标的影响。方法：雄性新西兰大耳白兔30只,随机平分为三组：正常对照组(Control 组)、CHF 模型组(CHF 组)和 CHF+VOL 组(VOL组)。CHF模型组经耳缘静脉推注异丙肾上腺素(0.3mg/kg/天,连续注射3周)诱导；Control组平行推注等体积生理盐水；VOL组对CHF兔持续静脉滴注浓度为50mg/L的 VOL。记录各组在体心脏左心室单相动作电位(MAP)主要参数静息膜电位(RMP)、动作电位幅度(APA)、动作电位最大上升速率(Maxdv/dt )和动作电位复极化恢复时程(APD10-90)；观察各组室性心律失常诱发周长(BCL)、诱发率和心律失常持续时间；分离单个心室肌细胞后,全细胞膜片钳技术记录心室肌细胞 L-型钙电流(ICa-L )及电流-电压(I-V)曲线。结果：与 Control 组比较,CHF 组RMP、APA、Maxdv/dt均明显降低,APD10、APD20、APD50和 APD90均显著延长(P 均<0.01)；与 CHF组比较,VOL组RMP、APA、Maxdv/dt均明显增加,各 APD时程均显著缩短(P<0.01)。CHF组诱发室性心律失常 BCL、心律失常诱发率和持续时间均大于Control组(P<0.01)；VOL组BCL、心律失常诱发率和持续时间均小于 CHF组(P<0.01)。当钳制电位为+20mV时,与 Control 组比较,CHF组心室肌细胞 ICa-L电流密度由(-12.13±0.99pA/pF)下降为(-7.14±0.33pA/pF)(P<0.01)；VOL组则较 CHF组 ICa-L电流密度明显上升(-10.86±0.50pA/pF)(P<0.01),VOL组 ICa-L的 I-V曲线较CHF组明显下移,接近 Control 组。结论：VOL 能显著降低 CHF心室肌电生理易损性和室性心律失常易感性,拮抗CHF室性心律失常；其机制可能与 VOL可增加心室肌细胞 ICa-L有关。