【摘要】 目的:观察缺血预处理对于大鼠部分肝移植术后肝再生信号通路的影响。方法:采用雄性Lewis大鼠建立50%体积肝移植,将120只大鼠随机分为对照组(C组)和缺血预处理组(IPC组),IPC组大鼠在体内切肝前接受10min肝血流阻断及随后15min的血液复流。分别在术后2、6、24、48h提取肝组织。观察术后两组生存率,提取血清测定谷丙转氨酶(ALT),ELISA法测肝组织中肿瘤坏死因子α(TNF-α),白细胞介素(IL-6)水平,免疫组化法测定肝细胞增殖核细胞抗原(PCNA)。Western blot测定肝脏中cyclin D1、CDK4、STAT3、磷酸化STAT3(P-STAT3)水平。结果:术后两组生存率比较无明显差别,术后ALT水平,IPC组在2、6h低于C组。TNF-α术后6hIPC组明显高于C组。IPC组的IL-6水平在术后2、6、24、48h均高于C组。PCNA显示术后IPC组阳性细胞数明显高于C组。cyclin D1蛋白在术后C组表达弱于IPC组。Cdk4蛋白在术后IPC组表达强于C组。STAT3蛋白术后两组表达相似。P-STAT3蛋白术后C组蛋白表达弱于IPC处理组。结论:经过缺血预处理的50%部分体积大鼠肝移植,IL-6、TNF-α诱导的肝再生信号通路增强,提示肝再生能力也增强。更多还原

【Abstract】 Objective:To evaluate the effects of ischemic preconditioning(IPC) on the signal transduction pathways of liverregeneration after partial liver transplantation in rat models. Methods:Male Lewis rats were used as donors and recipients of 50% orthotopic liver transplantations. 120 rats were divided into two groups randomly, control group(C) and ischaemic preconditioning treated group(IPC). IPC group was performed by clamping of the portal vein and hepatic artery of the donor for 10 minutes followed by reperfusion for 15 minutes before harvesting. The survival rate of both group were calculated each day up to 7 days. At 2,6,24, 48 h after reperfusion, serum Alanine Aminotransferase(ALT) of both group were measured, graft samples were obtained to determine the hepatic levels of TNF-α,IL-6 and PCNA. The expression of proteins cyclin D1,Cdk4,STAT3 and P-STAT3 were detected by Western blot. Results:After liver transplantation there was no significant difference between both groups on the survival rate. The level of serum ALT at 2 h and 6 h of IPC group lower than the control group. The hepatic levels of TNF-α of IPC group were higher than the control at 6 h. As to the IL-6, group C attenuated at all time spots. The activity of PCNA in IPC group increased significantly compared with the control as showed by Western blot. Cyclin D1 were expressed intensively in IPC group. The results of P-STAT3 were similarly to the Cyclin D1. Cdk4 were expressed intensively in IPC group. There was no difference between both group on STAT3. Conclusion:After 50%-size-graft liver transplantation, IPC can enhance the liver regeneration pathways induced by IL-6 and TNF-α,thus improve the ability of liver regeneration.更多还原