腺苷A2受体激动剂对大鼠胰腺缺血再灌注损伤时氧自由基和细胞凋亡的影响

Effect of adenosine A2 receptor agonist on oxygen free radicals and apoptosis during ischemia reperfusion injury in rat pancreas

目的:研究腺苷A2受体激动剂对大鼠胰腺缺血再灌注损伤时的氧自由基和细胞凋亡的影响.方法:大鼠随机分成3组(n=18),即假手术组、对照组和实验组,对照组和实验组大鼠脾下动脉钳夹30min,假手术组不进行缺血处理;三组再灌注前经阴茎背静脉分别注射生理盐水(2mL/kg)或A2受体激动剂CGS21680(300μg/kg);再灌注15min、30min和60min分别检测胰腺组织中脂质过氧化物(lipoperoxides,LPO)、细胞凋亡的变化以及观察胰腺组织的形态学变化.结果:再灌注15、30和60min后,对照组胰腺组织中LPO和细胞凋亡明显高于假手术组(LPO:8.25±1.15vs1.63±0.46,10.67±2.04vs1.85±0.62,15.31±3.02vs2.02±0.86,均P<0.05;细胞凋亡:0.55±0.08vs0.18±0.04,1.21±0.15vs0.20±0.06,2.63±0.52vs0.23±0.06,均P<0.05或0.01)和实验组(LPO:8.25±1.15vs6.51±1.38,10.67±2.04vs6.84±1.74,15.31±3.02vs10.22±2.91,均P<0.05;细胞凋亡:0.55±0.08vs0.32±0.16,P<0.05;1.21±0.15vs0.44±0.20,2.63±0.52vs0.50±0.43,均P<0.05或0.01);.对照组中,再灌注30min和60min同15min相比,前两者LPO、细胞凋亡增高明显,且差异有统计学意义(P<0.05orP<0.01).假手术组和实验组胰腺组织损伤不明显,而对照组胰腺组织随再灌注时间的延长损伤加重.结论:腺苷A2受体激动剂可减轻大鼠胰腺缺血再灌注损伤时氧自由基和细胞凋亡的发生,从而减轻胰腺缺血再灌注损伤.

AIM： To investigate the role of adenosine A2 receptor agonist in protection from production of oxygeon free radicals and induction of apoptosis during ischemia and reperfusion injury in rat pancreas. METHODS： The rats were divided randomly into sham, control and experimental groups. Af-ter 30 min clamping of subsplenic artery, normal saline （2 mL/kg body weight） or A2 receptor agonist CGS21680 （300 μg/kg body weight） was injected via dorsal penis vein, and at 15 min, 30 min and 60 min reperfusion, the changes of lipo-peroxides （LPO）, apoptosis and morphology in pancreas tissues were examined. RESULTS： After 15, 30 and 60 min reperfusion, LPO increased significantly in control group compared with the sham operation group （8.25 ± 1.15 vs 1.63 ± 0.46, 10.67 ± 2.04 vs 1.85 ± 0.62, 15.31 ± 3.02 vs 2.02 ± 0.86, all P 〈 0.05） and ex-perimental group （8.25 ± 1.15 vs 6.51 ± 1.38, 10.67 ± 2.04 vs 6.84 ± 1.74, 15.31 ± 3.02 vs 10.22 ± 2.91μmol/L, all P 〈 0.05）. Apoptosis increased significantly in control group compared with the sham operation group （0.55 ± 0.08 vs 0.18 ± 0.04, 1.21 ± 0.15 vs 0.20 ± 0.06, 2.63 ± 0.52 vs 0.23 ±0.06, P 〈 0.05 or 0.01） and experimental group （0.55 ± 0.08 vs 0.32 ± 0.16 P 〈 0.05; 1.21 ± 0.15 vs 0.44 ± 0.20, 2.63 ± 0.52 vs 0.50 ± 0.43, all P 〈 0.05 or 0.01）. In the control group, compared with 15 min reperfusion, LPO and apoptosis increased significantly at 30 min or 60 min reperfusion （P 〈 0.05 or 0.01）. In sham operation group and experimental group, no remarked damage of pancreas was detected, but in control group, the pancreas damage became more serious with the prolonging of reperfusion. CONCLUSION： Adenosine A2 receptor agonist attenuates postischemic production of oxygen free radicals and induction of apoptosis in pan-creas tissues, thereby minimizes the ischemia reperfusion injury.