к阿片受体选择性激动剂U50488H对大鼠心脏功能的影响

Effects of selective к-opioid receptor agonist U50488H on cardiac function of rats

目的:研究选择性к阿片受体选择性激动剂U50488H对大鼠心脏功能的影响,以探讨减少阿片肽类药物依赖性和成瘾性的可能性。方法:将实验大鼠按照随机原则分为对照组和U50488H组,观察大鼠心率,动脉压,左心室内压(leftventricularpressure,LVP)及心脏收缩、舒张功能(±dp/dtmax)等指标的变化情况。结果:U50488H在较大剂量时(1.5mg/kg)短时间内可以显著降低大鼠心率犤(302±9)次/min犦,动脉压犤(71±10)mmHg犦(1mmHg=0.133kPa),LVP犤(10.3±1.3)kPa犦,+dp/dtmax犤(386±46)kPa/s犦,-dp/dtmax犤(278±44)kPa/s犦,与对照组犤(392±12)次/min,(106±10)mmHg,(15.6±1.6)kPa,(516±63)kPa/s,(388±52)kPa/s犦比较,差异有显著性意义(t=20.329,12.075,14.513,15.331,P均=0.000),作用持久。结论:选择性к阿片受体选择性激动剂U50488H对大鼠心肌收缩具有明显的负性肌力作用,而且作用时间较为持久。

AIM:To investigate the effects of U50488H(a selective к opioid receptor agonist) on cardiac functions in rats in vivo,and to explore the possibility of reducing addiction and dependence of opioid drugs. METHODS:Experimental rats were randomly divided into control group and U50488H group,and the changes of heart rate(HR),arterial blood pressure(ABP),left ventricular pressure(LVP) and diastolic function(±dp/dtmax) were observed. RESULTS:Large dose of U50488H(1.5 mg/kg) could reduce the HR[(302±9)times per minute],ABP[(71±10)mmHg(1 mm Hg=0.133 kPa)],LVP(10.3±1.3)kPa],+dp/dtmax,+dp/dtmax[(386±46) kPa/s],-dp/dtmax[(278±44) kPa/s] in a short period,significantly different from those in the control group[(392±12)times per minute ,(106±10)mm Hg,(15.6±1.6)kPa,(516±63)kPa/s,(388±52)kPa/s](t=20.329,12.075,14.513,15.331,P=0.000),and the effect was long lasting. CONCLUSION:U50488H has an obvious negative inotropic effect on myocardial contraction in rats with long duration.