CAJ | 학술논문

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250～300 g,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),δ1受体特异性阻断剂(BNTX)组(B组)和δ1受体特异性阻断剂+激动剂组(BT组).经股动脉放血,10 min内使平均动脉压降至40 mm Hg,维持此水平,休克期60 min,复苏期120 min.HS组于复苏前即刻经左颈静脉输注生理盐水0.5 ml;T组于复苏前即刻静脉注射TAN-67 10 mg/kg;B组于复苏前即刻静脉注射BNTX 3 mg/kg;BT组于复苏前即刻静脉注射BNTX 3 mg/kg,10 min后静脉注射TAN-67 10 mg/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120 min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mPIP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mPTP开放,该作用可能为机体内源性保护机制之一.
목적 평개δ1수체재출혈성휴극대서심기손상중적작용.방법 성년웅성SD대서24지,체중250～300 g,수궤분위4조(n=6):출혈성휴극조(HS조)、δ1수체특이성격동제(TAN-67)조(T조),δ1수체특이성조단제(BNTX)조(B조)화δ1수체특이성조단제+격동제조(BT조).경고동맥방혈,10 min내사평균동맥압강지40 mm Hg,유지차수평,휴극기60 min,복소기120 min.HS조우복소전즉각경좌경정맥수주생리염수0.5 ml;T조우복소전즉각정맥주사TAN-67 10 mg/kg;B조우복소전즉각정맥주사BNTX 3 mg/kg;BT조우복소전즉각정맥주사BNTX 3 mg/kg,10 min후정맥주사TAN-67 10 mg/kg.기록심솔、평균동맥압、좌실압、좌실수축압최대상승속솔화좌실수축압최대하강속솔.급약후120 min시,처사대서관찰심기초미결구,병측정심기선립체통투성전환공(mPTP)적개방수량.결과 여HS조비교,T조평균동맥압화심공능지표승고,심기mPTP개방감소,B조mPIP개방증다(P<0.05),B조화BT조평균동맥압화심공능지표차이무통계학의의(P>0.05).T조심기초미결구손상교기여3조감경.결론 대서출혈성휴극치심기손상시,궤체가재일정정도상격활δ1수체,억제심기mPTP개방,해작용가능위궤체내원성보호궤제지일.
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% pentobarbital 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/dt_(max) 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 min 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 mitochoadria were isolated. The opening of mPTP was determined by spectrometry through the change in absorbance at 540 nm (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 can 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.