哇巴因对大鼠离体心功能作用的量-效关系

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目的:观察不同浓度哇巴因(ouabain,OUA)对大鼠离体心功能的影响。方法:SD雄性大鼠随机分成7组(n=6):正常组(NC组),OUA 10~(-9)mol/L组,OUA 10~(-8)mol/L组,OUA 10~(-7)mol/L组,OUA 10~(-6)mol/L组,OUA 10~(-5)mol/L组,OUA 10~(-4_mol/L组。左心室插管检测各组大鼠离体心脏血流动力学指标:左室峰压(LVSP)、心率(HR)、左室内压最大上升速率(+dp/dt_(max));观察各组大鼠的心律失常发生情况并进行心律失常评分;检测各组相同时间点的冠脉流出液中乳酸脱氢酶(LDH)的活性,同时测定各组心肌组织中Na~+-K~+-ATP酶的活性,HE染色观察各组大鼠心肌形态学变化。结果:同NC组相比,OUA10~(-9)mol/L组大鼠心脏LVSP×HR和+dp/dt_(max)无明显差异(P>0.05),OUA 10~(-8)mol/L和10~(-7)mol/L组大鼠心脏LVSP×HR和+dp/dt_(max)呈剂量升高而增强(P<0.05或P<0.01);OUA 10~(-9)mol/L、OUA 10~(-8)mol/L组的Na~+-K~+-ATP酶的活性明显升高(P<0.05或P<0.01);同NC组相比,OUA浓度在(10~(-6)~10_(-4))mol/L时,OUA对各组大鼠的心功能呈剂量依赖性抑制作用(P<0.01);各组大鼠的心律失常评分明显升高;各时间点心脏灌流液中LDH的活性亦明显升高,各组心肌组织Na~+-K~+-ATP酶活性均呈剂量依赖性降低(P<0.05或P<0.01)。结论:低浓度哇巴因[(10_(-9)~10~(-7))mol/L]对大鼠离体心脏有强心作用,但随着哇巴因浓度的升高[(10~(-6)~10~(-4))mol/L],转为对心脏呈剂量依赖性抑制作用。 Objective: To observe the effects of different concentrations of ouabain (OUA) on isolated rat heart function. Methods: SD male rats were randomly divided into 7 groups (n = 6): normal group (NC group), OUA 10 -9 mol / L group, OUA 10 -8 mol / L group, (-7 mol / L), OUA 10 ~ (-6) mol / L, OUA 10 ~ (-5) mol / L and OUA 10 ~ (-4 mol / L) Rat isolated heart hemodynamics indicators: left ventricular peak pressure (LVSP), heart rate (HR), maximum rate of left ventricular pressure rise (+ dp / dt max); observed in each group of rats arrhythmia And the arrhythmia score was measured. The activity of lactate dehydrogenase (LDH) in the coronary effluent was detected at the same time point. At the same time, the activity of Na ~ + -K ~ + -ATPase in myocardium of each group was measured. HE staining The morphological changes of myocardium in each group were observed.Results: Compared with NC group, LVSP × HR and + dp / dt max of OUA10-9 mol / L group had no significant difference (P> 0.05) LVSP × HR and + dp / dt max increased with increasing dose in OUA 10 -8 mol / L and 10 -7 mol / L groups (P 0.05 or P 0.01 ) Activity of Na ~ + -K ~ + -ATPase in 10 ~ (-9) mol / L OUA and 10 ~ (-8) mol / L OUA groups was significantly increased (P <0.05 or P <0.01); Compared with NC group, OUA had a dose-dependent inhibition on cardiac function in rats with OUA concentration of (10 -6 - 10 4) mol / L (P <0.01). The arrhythmia score of rats in each group was significantly higher than that of the control group (P <0.01). The activities of LDH in cardiac perfusate were significantly increased at all time points. The activities of Na ~ + -K ~ + -ATP (P <0.05 or P <0.01) .Conclusion: Low concentration of ouabain [(10 9 -9 10 -7 mol / L) has a strong cardiac effect on rat isolated heart However, as the concentration of ouabain increased ([10 ~ (-6) ~ 10 ~ (-4)) mol / L], it turned into a dose-dependent inhibition on the heart.
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