吗啡对大鼠心肌缺血/再灌注损伤的保护作用

The protective effects of morphine on ischemic reperfusion myocardium in rats

目的 探讨吗啡对离体大鼠心肌缺血/再灌注损伤的保护作用和机制。方法 建立离体大鼠心脏灌注模型。TTC染色梗死心肌。观察缺血/再灌注后,吗啡对冠脉流量（CF）、心率（HR）、左室压力（LVP）、左室压力最大变化速率（LVP/dtmax）及心梗范围的影响,并观察纳洛酮和glibenclamide对吗啡作用的影响。结果 缺血/再灌注后,离体大鼠心脏的CF、HR、LVP和LVP/dtmax显著下降（P<0.01）。缺血前给予吗啡可以使缺血/再灌注后HR、LVP和LVP/dtmax显著恢复（P<0.01）,心梗范围显著缩小（P<0.01）。吗啡不能增加缺血/再灌注后离体大鼠心脏的CF（P>0.05）。分别给予纳洛酮和glibenclamide可以完全取消吗啡的心肌保护作用。结论 吗啡可以减轻大鼠心肌的缺血/再灌注损伤。吗啡是通过心肌局部的阿片受体及心肌细胞的KATP通道介导产生心肌保护作用。

Objective To investigate the protective effects of morphine on ischemic reperfusion myocardium in vitro and the underlying mechanism. Methods Forty male Wistar rats weighing 280-330g were anesthetized with intra-peritoneal pentobarbital 30mg·kg-1 . Chest was opened and heart removed. The isolated heart was perfused with oxygenated Krebs-Hensleit( K-H) buffer solution (95 % O2, 5 % CO2 ) in a Langendorff apparatus. The animals were randomly divided into five groups with 8 animals in each group : (l)control group; (2)ischemia-reperfusion (I/R) group in which ischemia lasted 30 min followed by 40min reperfusion; (3) in morphine pretreatment group the isolated heart was perfused with K-H buffer solution containing morphine 0.3μmol/L for 20min before I/R; (4) morphine-naloxone group for 20min; (5) morphine-glibenclamide group in which before I/R the isolated heart was perfused with K-H solution containing morphine 0.3μ/mol/L and glibenclamide 10mol/L for 20 min. Left ventricle developed pressure (LVP) and LVP/dtmax were measured from a water-filled latex balloon inserted in LV. Heart rate was determined by an epicardial ECG. The size of myocardial infarct was determined by TTC. Coronary flow (CF) was collected and recorded. LVP, LVP/dtmax, HR and CF were recorded before ischemia, and at 10, 20,30,40 min during reperfusion. Results After I/R CF, HR, LVP and LVP/dtmax of the isolated hearts were decreased significantly (P<0.01). When morphine was perfused before ischemia HR, LVP and LVP/dtmax were increased significantly (P<0.01) and infarct size was reduced (P<0.01). Morphine did not increase CF after I/R (P>0.05) . The cardioprotective effects of morphine were abolished by naloxone or glibenclamide completely. Conclusion Morphine can reduce I/R injuries to isolated rat heart. The cardioprotective effects of morphine are mediated via local opioid receptor and KATP channel.