缺血预处理对大鼠小体积供肝的保护作用及机制

Protective effect of ischemic preconditioning on rat small-for-size liver graft and its mechanism

目的探讨缺血预处理(IPC)对大鼠小体积供肝的保护作用及其机制。方法120只SD大鼠随机分为3组(每组20对):无热缺血组(NWI)、缺血再灌注组(WI)和缺血预处理组(IPC)。用双袖套法建立大鼠小体积肝移植模型。各组10只受体大鼠于术前1 d、术后1、2、3、5 d取血,用自动生化分析仪检测AST和ALT。NWI组于供肝灌注前及植入后0．5、1、2、3 h,WI组于热缺血前及植入后0．5、1、2、3 h,IPC组于IPC前、IPC后及植入后0．5、1、2、3 h取肝组织,用硝酸还原法检测其NO浓度。结果IPC可降低大鼠小体积肝移植术后血清AST和ALT浓度,提高再灌注早期肝脏组织NO的浓度,降低再灌注晚期肝脏组织NO的浓度(P<0．05)。结论NO在大鼠肝脏的缺血再灌注损伤中可能具有双重作用。IPC对大鼠小体积供肝的缺血再灌注损伤有保护作用。其机制可能是通过促进供肝再灌注后早期NO合成,改善肝脏微循环,同时抑制供肝再灌注后晚期NO合成,减轻过量NO的损伤作用,从而保护移植肝脏功能。

Objective To investigate the effect of ischemic preconditioning on rat small-for-size liver graft and explore its mechanism. Methods A total of 120 SD rats were randomized into the nonwarm ischemia group （NWI, n=40）, warm ischemia group （WI, n=40） and ischemic preconditioning group （IPC, n=40）. The model of rat small-for-size liver transplantation was established by twocuff technique. The serum levels of ALT and AST were determined by the automatic biochemical analyzer ld before and 1, 2, 3 and 5 d after the operation. Hepatic tissue （0. 5 g） was procured before perfusion and 0. 5, 1, 2 and 3 h after transplantation in NWI group, before warm ischemia and 0. 5, 1, 2, and 3 h after transplantation in WI group, before and after IPC and 0. 5, 1, 2 and 3 h after transplantation in IPC group. Their NO density was determined with nitrose reduction. Results IPC decreased serum levels of AST and ALT after rat small-for-size liver transplantation, increased hepatic NO density in the early stage but reduced it in the late stage after reperfusion. Conclusions NO might play dual role in the ischemia and reperfusion injury of the rat liver. IPC can protect rat small-for-size liver graft from ischemia and reperfusion injury. The mechanism of which might be that IPC promotes NO synthesis of the liver graft in the early stage after reperfusion and improves hepatic microcirculation. Meanwhile, it inhibits NO synthesis of the liver graft in the late stage after reperfusion and alleviates the injury mediated by excessive NO.