甘松新酮对快速性心律失常大鼠心肌细胞抑制作用的实验研究

Experimental study on the inhibitory effect of nardosinone on myocardial cell in rats with tachyarrhythmia

目的研究甘松新酮对快速性心律失常大鼠心肌细胞的抑制作用。方法用数字表法将60只健康成年雄性Wistar大鼠随机分为正常组、模型组及甘松新酮组,各20只。模型组、甘松新酮组大鼠舌下静脉注射0.002%乌头碱1 m L·kg-1,建立快速性心律失常动物模型。甘松新酮组大鼠腹腔注射甘松新酮100μg·g-1(约0.5 m L);正常组、模型组大鼠腹腔注射等量生理盐水。用多导电生理记录仪测量各组大鼠的心率、血流动力学及心系数指标,用激光共聚焦显微镜测量心肌细胞钙离子,放免法、凝胶成像法检测环磷酸腺苷(c AMP)及蛋白激酶A(PKA)变化。结果正常组,心率、左心室终末舒张压(LVEDP)、心系数及Ca2+水平显著低于模型组(P<0.05),其左心室收缩压(LVSP)、+dp/dtmax、-dp/dtmax均显著高于模型组(P<0.05);甘松新酮组,上述指标较模型组有明显改善(P<0.05)。正常组,心肌组织c AMP、PKA水平显著低于模型组(P<0.05);正常组与甘松新酮组的依赖蛋白激酶(c AMP)、激酶A(PKA)水平无明显差异(P>0.05)。结论甘松新酮可通过影响c AMP-PKA细胞信号转导通路,促进心功能的恢复,抑制心肌细胞钙超载,能够明显改善快速性心律失常大鼠心律。

Objective To investigate the inhibitory effect of nardosinone on myocardial cell in rats with tachyarrhythmia. Methods A total of 60 healthy adult male Wistar rats were randomly divided into normal group, model group and nardosinone group with 20 rats in each one. The 0. 002% aconitine 1 mL ·kg^-1 was used to treat rats in model group and nardosinone group. After the establishment of tachyarrhythmia animal model, 100 μg·g^-1（about 0. 5 mL） nardosinone was used to treat rats in nardosinone group by intraperitoneal injection. Heart rate, hemody- namics and heart coefficient index were measured using multi -conduc- tive physiological recorder. Calcium ion （Ca^2＋ ） in myocardial cell was measured using laser confoeal microscope. Cyclic adenosine monophos- phate （cAMP） and protein kinase A （PKA） changes were detected using radioimmunoassay and gel imaging. Results In the normal group, heart rate, left ventricular end -diastolic pressure （LVEDP）, heart coefficient, Ca^2＋ level were significantly lower than those of model group. And the left ventricular systolic pressure （LVSP） , ＋ dp/dtmax,- dp/dtmax were significantly higher than those in of model group （P 〈 0.05 ）. Compared with the model group, the a- bove indicators have been improved in nardosinone group （ P 〈 0. 05 ）. In the normal group, myocardial cyclic adeno- sine monophosphate（ cAMP）, PKA level was significantly lower than those of model group （P 〈 0.05 ）. Difference of cAMP and PKA between normal group and nardosinone group was not significant （P 〉 0. 05 ）. Conclusion Nardosi- none can affect the signal transduction pathway of cAMP - PKA cells, promote the recovery of cardiac function and in- hibit calcium overload in myocardial cells, thus significantly improving the heart rate in rats with cardiac arrhythmia.