U50488H联合东莨菪碱对大鼠离体心脏的保护作用

Protective effects on isolated rat heart preservation by US0448H and scopolamine

目的探讨κ阿片受体激动剂US0488H联合东莨菪碱对大鼠离体心脏低温保存的保护效果其作用机制。方法54只SD大鼠随机分为9组，每组6只，用U50488H、东莨菪碱及KATP阻断剂（5-HD）组合后进行心脏保存。采用Langendorff心脏灌注和工作模型装置进行心脏功能测定，比较低温保存6h后心功能恢复率、心肌含水量、能量变化，观察心肌超微结构改变。结果US0488H＋东莨菪碱组左心室功能和结构损伤最轻，单用U50488H、东莨菪碱、St．Thomas液组左心室功能和结构损伤较轻，而对照组左心室功能和结构损伤严重；U50488H＋东莨菪碱组心功能恢复率最快、细胞ATP含量最高，其次是单用U50488H、东莨菪碱、St．Tnomas液组。加用5．HD时，US0488H＋东莨菪碱组合各项指标变化不显著，但单用U50488H、东莨菪碱组各项指标变化显著，差异也有统计学意义（P〈0．05）。结论US0488H、东莨菪碱对大鼠离体心脏在6h内有明显的保护作用，达到St．Thomas液水平，两者联合使用时效果更佳。开放mitoKATP通道可能是发挥保护作用的重要机制。

Objective To study the protective effects on isolated rat heart preservation by kappa-opioid receptor activation （U50448H） and scopolamine. Methods SD rats （n = 54） were randomly divided into nine groups （n = 6 in each group ）, their heartswere preserved with K-H （control group）, U50448H, scopolamine （Sco）, U50448H ＋ Sco, 5-hydr-oxydecanoate （5-HD）, U50448H ＋ 5-HD, Sco ＋ 5-HD, U50448H ＋ Sco ＋ 5-HD and St.Thomas （STH） solution respectively for 6 hours. The isolated hearts were perfused in the Langendorff rat mode for functional evaluation before and after preservation. After reperfusion, some indexes were measured, including the left ventricular function recovery as percentage （ ＋ dp/dtmax ）, contents of adenosine triphesphateand wet weights in myocardium, ultrastructure changes in myocardium were also observed by electron microscope. Results In U50448H and Sco group, theimpairment of the left ventricle function and ultrastructure was minimal, that in US0448H, Sco, STH groups was mild, while that in K-H groups was severe. US0448H ＋ Sco group offered the fastest dp/dt max, and had the highest ATP content of myocardinm. While adding 5-HD in the preservation solutions, there were no significant differences in U50448H ＋ Sco group, but the differences were significant in US0448H or Sco group. Conclusion Kappa-opioid receptor activation （US0448H） and scopolamine can protect isolated rabbit heart for 6 hours effectively, the recovery of heart function and the protection of structure by US0448H or by scopolamine are similar to that by St. thomas solution. The protective effects may be mediated by ATP-sensitive K^＋ channels. Also, U50448H has more beneficial protective effects when cmbined with scopolamine.