缺血后处理对大鼠肝大部切除后残肝缺血再灌注损伤的影响

目的探讨缺血后处理对肝大部切除后残肝缺血再灌注损伤的影响。方法选取健康清洁级雄性SD大鼠115只,体重230～280g,其中25只随机分为5组:70%单纯肝切除1组(PH1)、70%肝切除合并缺血再灌注1组(PHIR1)、10s-10s循环3次后处理组(IPO1)、30s-30s循环3次后处理组(IPO2)和60s-60s循环3次后处理组(IPO3)。再灌注6h后取各组大鼠下腔静脉血及残肝组织,测定血清ALT、AST活性及肝细胞凋亡指数,选取保护效果最佳的后处理方案。剩余90只大鼠随机分为3组:PH2组、PHIR2组和IPO组,并于再灌注1、6、12、24、48h取各组大鼠下腔静脉血及残肝组织,每时点6只,测定血清ALT、AST活性及肝组织丙二醛(MDA)、超氧化物岐化酶(SOD)、髓过氧化物酶(MPO)水平。结果与PH1组比较,PHIR1组、IPO1组、IPO2组和IPO3组血清ALT和AST活性、肝细胞凋亡指数均升高(P<0.05);与PHIR1组比较,IPO1组、IPO2和IPO3组血清ALT和AST活性、肝细胞凋亡指数均降低,但仅IPO2组差异有统计学意义(P<0.05)。选择IPO2组作为后处理方案,与PHIR2组比较,IPO组各时点ALT、AST活性和MDA、MPO表达水平降低(P<0.05),SOD表达水平升高(P<0.05)。结论缺血后处理可以减轻肝大部切除后残肝的缺血再灌注损伤,其机制与抑制氧化反应,减少自由基生成,减轻炎细胞浸润等有关。

Effect of ischemic postconditioning on ischemia reperfusion injury of the remnant liver after major hepatectomy

Objective To explore the effect of ischemic postconditioning on ischemia reperfusion injury of the remnant liver after major hepatectomy.Methods One hundred and fifteen healthy male Sprague-Dawley rats of clean grade,weighing 230-280 g,were selected.Twenty-five of them were chosen to be assigned randomly into five groups: 70% simple hepatectomy group(PH1),70% hepatectomy combined with ischemia reperfusion group(PHIR1),three cycles of 10 s-10 s ischemic postconditioning group(IPO1),three cycles of 30 s-30 s ischemic postconditioning group(IPO2) and three cycles of 60 s-60 s ischemic postconditioning group(IPO3).The inferior vena blood and the remnant liver tissues were harvested 6 h after reperfusion to be detected for serum ALT and AST activities and apoptosis index(AI) of hepatocytes to screen the optimal regimen with the best protection.The remaining 90 rats were randomly divided into three groups: PH2,PHIR2 and IPO groups.The inferior vena blood and the remnant liver tissues were harvested at 1,6,12,24 and 48 h after reperfusion in each group,6 rats at each time point.Serum ALT and AST activities and hepatic tissue levels of MDA,SOD and MPO were determined.Results Compared with those in PH1 group,serum ALT,AST activities and hepatocyte AI in PHIR1,IPO1,IPO2 and IPO3 groups were all increased(P<0.05).Compared with those in PHIR1 group,serum ALT,AST activities and AI in IPO1,IPO2 and IPO3 groups were all decreased but had a significant difference only in IPO2 groups(P<0.05).The treatment of IPO2 was determined as the postconditioned regimen of the subsequent experiment. The latter results showed that serum ALT,AST activities as well as levels of MDA and MPO decreased but SOD increased at each time point in IPO group in comparison with PHIR2 group(P<0.05). Conclusion Ischemic postconditioning can attenuate ischemia reperfusion injury of the remnant liver after major hepatectomy,and its mechanism is related to inhibiting oxidative stress as well as reducing production of free radicals and infiltration of inflammatory cells.