论文部分内容阅读
目的 研究肝脏缺血预处理(经典缺血预处理IPC)的第一保护窗(FW)与肢体缺血预处理(远端缺血预处理RPC)的第二保护窗(SW)及两者联合应用对大鼠肝脏缺血再灌注(I/R)损伤的保护作用及可能机制.方法 大鼠随机分成5组:I/R组不行预处理;IPC组以肝缺血5 min行顶处理;RPC组以双后肢缺血5 min,反复3次行预处理;RPC+IPC组先行RPC,24 h后行IPC作预处理;S组仅行开腹,不行其他处理.3个预处理组及I/R组均行肝缺血1 h再灌注3 h.取血用于血清谷丙转氨酶(ALT)与血清谷草转氨酶(AST)检测.切取肝组织用于测定肿瘤坏死因子α(TNF-α)和热休克蛋白70(HSP70)的表达、湿干比(W/D)及观察显微、超微结构的变化.结果 与I/R组比较,IPC组,RPC组及RPC+IPC组ALT,AST,W/D及TNF-α阳性表达均明显降低(P＜0.01),HSP70表达量明显增加(P＜0.01),肝脏的显微及超微结构损伤减轻;IPC,RPC,RPC+IPC组3组间各项指标差异无统计学意义(P＞0.05).结论 IPC的FW,RPC的SW及两者联合应用对大鼠肝脏I/R损伤均有明显的保护作用,三者在保护强度上无明显差异.其机制可能与抑制TNF-α的产生、诱导保护性蛋白HSP70的表达、减轻肝脏水肿、改善肝组织微循环有关.“,”Objective To investigate the protective effect of the fast window (FW) of liver ischemic preconditioning (IPC),the second window (SW) of remote (leg) ischemic preconditioning (RPC) and conbined applications of liver and lges IPC to against liver ischemia/reperfusion (I/R) injury in the rat,and to investigate the mechanism of the protection.Methods Rats were randomly divided into five groups (n = 8 each):(1) Sham group (S group),rats without IPC,(2) Rats with 5 min IPC (IPC group);(3) Rat wiht both liver and lower limbs IPC and repeated three times (RPC group);(4) IPC 24 h after RPC group;(5) IR without IP (I/R group);except S group,the rats were subjected to 60 min sustained liver ischemia followed by 180 min reperfusion.All ischemia rats were only subjected to 70% liver ischemia.Finally,blood and liver samples were obtained to determine the activity of ALT and AST,the expressions of TNF-α and HSP70 protein,and liver wet/dry weight (W/D) and pathology.Results All IPC group and RPC group and IPC + RPC group had obviously lower levels of ALT,AST,W/D,TNF-α than that of the I/R group (P ＜0.01),but had obviously higher expressions of HSP70 protein than the I/R group (P ＜ 0.01),howerer,all the indices between IPC group and RPC group and IPC + RPC group had no statistical difference (P ＞ 0.05).Conclusions The FW of the IPC,the SW of the RPC and combined applications can lessen hepatic I/R injury.There is no significant difference in the protective intensity of the 3 motheds.The protective effects possibly are due to suppression of TNF-α production,induction of protein HSP70 expression and improvement of liver microcirculation.