PI3K／AKT信号通路在异丙酚减轻离体大鼠心脏缺血再灌注损伤中的作用

Role of PI3K/AKT signaling pathway in the protective effect of propofol on isolated rat heart against ischemia-reperfusion injury

目的 探讨PI3K／AKT信号传导通路在异丙酚减轻离体大鼠心脏缺血再灌注损伤中的作用。方法 成年SD大鼠32只，随机分为4组：缺血再灌注组（I／R组）、异丙酚组（P组）、渥曼青霉素组（W组）和异丙酚＋渥曼青霉素组（PW组），每组8只。建立Langendorff离体心脏灌注模型，灌注压10kPa,灌注速率7．10ml／min，I／R组用K-H液灌注，P组用含50μmol／L异丙酚的K-H液灌注，W组用含100nmol／L渥曼青霉素的K-H液灌注；PW组用含50μmol／L异丙酚＋100nmol／L渥曼青霉素的K-H液灌注，灌注15min，全心缺血30min，再灌注60min。测定再灌注10、40min时冠脉流出液中心肌肌钙蛋白（cTnI）浓度，再灌注60min时测定心肌组织丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性，电镜下观察心肌细胞超微结构。结果 与I／R组比较，P组再灌注期间cTnI浓度明显降低，心肌组织SOD活性升高，MDA含量降低（P〈0．05），其余2组上述指标差异无统计学意义（P〉0．05）；与缺血前比较，P组再灌注40min时cTnI浓度升高，其余各组再灌注期间cTnI浓度均升高（P〈0．05或0．01）。P组电镜下心肌超微结构改变减轻。结论 异丙酚减轻离体大鼠心脏缺血再灌注损伤可能通过PI3K／AKT信号传导通路介导。

Objective To investigate the role of PI3K/AKT signaling pathway in the protection of isolated rat heart from ischemia-reperfusion （I/R） injury by propofol. Methods Thirty-two adult SD rats weighing 200-300 g were anesthetized with intrapefitoneal urethane. The chests were opened and hearts were excised and passively perfused in a Langendorff apparatus with Krebs-Henseit buffer （KHB） saturated with 95% 02-5% CO2 at 4℃. The isolated hearts were made globally ischemic for 30 min followed by 60 min reperfusion and were perfused with plain KHB （ group I/R） or KHB containing propofol 50 μmol/L （ group P） or wortmannin 100 nmol/L （ group W） or propofol 50 μmol/L ＋ wortmannin 100 nmol/L （group PW）. The cardiac troponinI（cTnI） concentration in coronary effluent was detected before ischemia and at 10 and 40 min of reperfusion. The SOD activity and MDA content in myocardium were measured and ultrastructure of myocardium was examined by electron microscopy at the end of 60 min reperfusion. Results The cTnI concentration in coronary effluent was significantly lower during reperfusion in group P than in I/R group. The SOD activity was significantly increased while MDA content was significantly decreased in myocardium in propofol group as compared with I/R group. There was no significant difference in cTnI concentration in coronary effluent and SOD activity and MDA content in myocardium between group I/R, W and PW. Electron microscopy revealed that myocardial damage was significantly attenuated in propofol group. Conclusion PI3K/AKT signal transduction pathway may be involved in the protective effect of propofol on myocardium from I/R injury.