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...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。展开更多
Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to i...Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.展开更多
文摘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。
基金The study was supported by grants from National Natural Science Foundation of Chinathe Science and Technology committee of Shanghai Municipality(02JC14038).
文摘Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.
