摘要
目的初步探讨咪达普利对舒张功能不全心衰(DHF)大鼠心室肌细胞钠通道电流改变的影响。方法 50只雄性SD大鼠,随机分组:对照组、DHF组、咪达普利1.5 mg组(A1组)、3 mg组(A2组)和6 mg组(A3组)。采用腹主动脉缩窄建立DHF型,对照组只开腹和分离腹主动脉。A1-A3组大鼠术后灌胃给予咪达普利1.5、3、6 mg/(kg·d);对照组和DHF组大鼠灌胃给予同等量的生理盐水。4周末心脏超声检测心功能,颈动脉插管检测血流动力学,标准全细胞膜片钳技术记录通道电流。结果①与对照组比较,DHF组大鼠IVS、LVPW、LVM、SBP、DBP、LVSP和LVEDP升高,Tau延长,LV-dp/dtmax下降;咪达普利降低DHF大鼠IVS、LVPW、LVM、SBP、DBP、LVSP和LVEDP,缩短Tau,升高LV-dp/dtmax,该作用随咪达普利剂量增加而增大;各组大鼠LVEDs、LVEDd、LVEF、心率和LV+dp/dtmax无明显差异;②与对照组比较,DHF大鼠心室肌细胞膜电容明显增大,心室肌细胞INa峰值电流密度明显增加,激活、失活和复活动力学特征未发生改变;咪达普利降低DHF大鼠心室肌细胞膜电容和INa峰值电流密度,使失活加快,该作用随着咪达普利剂量的增加而增大;咪达普利不影响DHF大鼠心室肌细胞激活和复活动力学特征。结论咪达普利降低舒张功能不全心衰大鼠心室肌INa峰值电流密度,使失活加快,该作用具有剂量依赖性。
[ Objective ] To study the effects of imidapril on sodium current in ventrieular myocytes of rats with di- astolic heart failure. [Methods] 50 SD rats were randomly divided into 5 groups： control group, DHF group, imi- dapril 1.5 mg group （A1 group）, 3 mg group （A2 group） and 6 mg group （A3 group）. DHF model was produced by abdominal aortic coarctation in the rats in DHF group and imidapril groups. The rats in imidapril groups were treat- ed with imidapril at the does of 1.5, 3 and 6 mg/（kg＇d） by intragastric administration, the others were treated with e- qual isotonic Na chloride. After 4 weeks, the cardiac function was assessed by echocardiography, the hemorheology was assessed l）y carotid arterial catheterization and INa was measured by whole-cell patch-clamp technique. [Re- suits ] （2）Compared with control group, interventricular septum （IVS）, left ventrieular posterior wall（LVPW）, left ven- tricular mass （LYM）, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, left ventricular systolic pressure （LVSP）, left ventricular end-systolic pressure （LVEDP） and the time constant for left ventrieular relaxation （Tan） were significantly higher, while maximum descent ratio for average left ventricular pressure （-dp/dtmax） were signifi cantly lower in DHF rats. Compared with DHF group, IVS, LVPW, LVM, SBP, DBP, LVSP, LVEDP and Tau were significantly lower,while -dp/dt~ was significantly higher in imidapril groups. These effects were increased accord- ing to the increasing dose of imidapril. There was no statistical significance in left ventricular end-diastolic diameter （LVEDd）, left ventricular end-systolic diameter （LVEDs）, left ventricular ejection fraction （LVEF）, heart rate and the maximum ascendsus ratio for average left ventricular pressure （＋dp/dtmax） among five groups. （2）Compared with control group, membrane capacitance （Cm） and the peak density of ventricular INa were significantly higher in DHF rats. While activation curves, recovery curves and inactivation curves were not changed. Compared with the DHF group, ventricular Cm and the peak density of ventricular INa were significantly lower in imidapril groups. And imidapril also made inactivation curves shift to more negative potentials in DHF rats. The effects of imidapril on sodium cur＇ rents were increased according to the increasing dose of it. Imidapril did not change activation curves and recovery curves. [ Conclusion ] lmidapril decreases the peak density of ventricular INa and made inactivation curves shift to more negative potentials in DHF rats, which increased in DHF rats with the increasing does of imidapril.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2013年第28期6-10,共5页
China Journal of Modern Medicine
基金
国家自然科学基金(No:30900625)
关键词
咪达普利
舒张功能不全
心肌细胞
膜片钳
钠通道
imidapril
diastolic heart failure
myocardial cell
patch clamp
sodium current
