摘要
目的:探究阿霉素诱导的低龄鼠扩张型心肌病(dilated cardiomyopathy,DCM)模型中心室肌细胞钠电流(sodium current,I_(Na))的变化。方法:将40只健康的两周龄SD大鼠随机平均分为DCM组(n=20)和对照组(n=20)。DCM组予腹腔注射阿霉素1 mg/kg每周2次,连续6周,诱导建立DCM模型,对照组给予等量生理盐水腹腔注射,以酶解法分离得到单个心室肌细胞,通过全细胞膜片钳技术记录I_(Na)、电流-电压(I-V)曲线和钠通道激活、失活和复活的变化情况。结果:与对照组比较,DCM组I_(Na)呈电压依赖性减小,I-V曲线上移,I_(Na)电流密度明显下降[(47.370±4.118)p A/p F vs.(64.310±3.278)pA/pF,P=0.003];钠通道激活过程减慢,稳态激活曲线右移,半数稳态激活电压明显升高[(-48.441±0.966)m V vs.(-55.132±0.945)m V,P=0.000];失活过程加快,稳态失活曲线左移,半数稳态失活电压降低[(-98.490±1.152)m V vs.(-90.700±1.983)m V,P=0.003];稳态复活曲线与对照组相比无统计学差异(P=0.617)。结论:阿霉素诱导的低龄DCM模型鼠心室肌细胞I_(Na)电流密度显著减少,钠通道激活过程减慢,失活过程加快,降低了I_(Na),DCM中传导阻滞的发生可能与此有关。
Objective:To investigate the changes in sodium current(I_(Na))of ventricular myocytes in young rats with doxorubicin-induced dilated cardiomyopathy. Methods:Forty SD rats of two-week-old were randomized divided into DCM group(n=20)and control group(n=20). Dilated cardiomyopathy was induced by intraperitoneal injection of doxorubicin 1mg/kg twice a week for six weeks;rats in control group received the injection of normal saline in the same dose. Single ventricular myocyte was isolated from rat heart by enzymatic dissociation and patch clamp technique was used to record the changes of I_(Na)in the left ventricular myocytes. Results:The I_(Na)of DCM group was potential-dependently reduced,the I-V curve was shifted to upward,and the I_(Na)current density in ventricular myocytes was significantly lower in DCM rats than in control rats[(47.370±4.118)p A/p F vs.(64.310±3.278)p A/p F,P=0.003].DCM inhibited the steady-state activation. The half activation potential was raised in DCM rats than in control rats[(-48.441±0.966)m V vs.(-55.132 ± 0.945) m V,P =0.000]. DCM accelerated the inactivation process. The half inactivation potential was lower in DCM group rather than in control group[(-98.490±1.152)m V vs.(-90.700±1.983)m V,P=0.003)]. The recovery process of I_(Na) was unchanged(P=0.617). Conclusion:Doxorubicin-induced DCM can significantly inhibit the steady-state activation,accelerate the inactivation,and decrease I_(Na)current density. These changes might lead to cardiac conduction block in DCM.
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2016年第9期923-927,共5页
Journal of Chongqing Medical University
基金
重庆市卫计委重点资助项目(编号:2012-1-047)
关键词
钠通道
扩张型心肌病
膜片钳
Sodium channels
Dilated cardiomyopathy
Patch clamp