δ1受体在出血性休克大鼠心肌损伤中的作用

Role of δ1 receptor in myocardial injury in a rat model of hemorrhagic shock

目的评价δ1受体在出血性休克大鼠心肌损伤中的作用。方法成年雄性SD大鼠24只，体重250．300g，随机分为4组（n=6）：出血性休克组（HS组）、δ1受体特异性激动剂（TAN－67）组（T组）、拭受体特异性阻断剂（BNTX）组（B组）和拭受体特异性阻断剂＋激动剂组（BT组）。经股动脉放血，10min内使平均动脉压降至40mmHg，维持此水平，休克期60min，复苏期120min。HS组于复苏前即刻经左颈静脉输注生理盐水0．5ml；T组于复苏前即刻静脉注射TAN－67 10mg／kg；B组于复苏前即刻静脉注射BNTX3mg／kg；BT组于复苏前即刻静脉注射BNTX3mg／kg，10min后静脉注射TAN-67 10mg／kg.记录心率、平均动脉压、左室压、左室收缩压最大上升速率和左室收缩压最大下降速率。给药后120min时，处死大鼠观察心肌超微结构，并测定心肌线粒体通透性转换孔（mPTP）的开放数量。结果与HS组比较，T组平均动脉压和心功能指标升高，心肌mPTP开放减少，B组mPTP开放增多（P〈0．05），B组和BT组平均动脉压和心功能指标差异无统计学意义（P〉0．05）。T组心肌超微结构损伤较其余3组减轻。结论大鼠出血性休克致心肌损伤时，机体可在一定程度上激活δ1受体，抑制心肌mPWP开放，该作用可能为机体内源性保护机制之一。

Objective To investigate the role of δ1 receptor in myocardial injury in a rat model of hemorrhagic shock. Methods Twenty-four male adult SD rats weighing 250-300 g were randomly divided into 4 groups （ n = 6 each） ： group I hemorrhagic shock （group HS） ; group II TAN-67 （group T） ; group III BNTX （group B） and group IV BNTX ＋ TAN-67 （group BT）. The animals were anesthetized with intraperitoneal （IP） 3 % pentoharbital sodium 30 mg/kg and tracheostomized. Spontaneous breathing was kept. Right and left femoral arteries were cannulated for MAP monitoring and blood withdrawal and reinfusion. Left jugular vein was cannulated for fluid and drug administration. ECG was continuously monitored. Left ventricular pressure （LVP） and ＋ dp/dtmax were recorded. Acute hemorrhagic shock was induced according to Wiggers modified technique. MAP was maintained at 40 mm Hg for 60 min. The removed blood was then reinfused for resuscitation. At the end of 60 rain of shock the animals received TAN-67 （a δ1 receptor specific angonist） 10 mg/kg and/or BNTX （a δ1 receptor specific antagonist） 3 mg/kg. At the end of 2 h of resuscitation the animals were killed and myocardial mitochondria were isolated. The opening of mPTP was determined by spectrometry through the change in absorbance at 540 mn （ A540 ）. Morphological changes in myocardium were detected by electron microscopy. Results The BP was significantly higher and cardiac function better in group T than in group HS. The opening of mPTP were significantly decreased in group T as compared with group B （P 〈 0.05 ）. The opening of mPTP were significantly increased in group B as compared with group HS （ P 〈 0.05 ）. The myocardial injury was attenuated in group T. The myocardial protective effect of TAN-67 was abolished by BNTX. Conclusion δ1 receptor ean be activated to some extent and then the opening of mPTP is inhibited during hemorrhagic shock-induced myocardial injury in rats, which may be one of the endogenous protective mechanisms.