低氧预适应诱导肝脏HIF-1α高表达对自体原位肝移植大鼠JNK信号转导通路的影响  

Effects of hypoxia inducible factor-lα with high expression mediated by hypoxia precondition on the JNK signaling pathway in rats received orthotopic liver autotransplantation

作　　者：孟中良[1] 田明祥[1] 张培建[1] 张杰[1] 庄卓男[1] 苏辉[1] 伍学艳[1] 金成 

机构地区：[1]扬州大学第二临床医学院普通外科研究室,225000 [2]无锡三院肝胆胰中心,214000

出　　处：《中华消化外科杂志》2011年第4期282-285,共4页Chinese Journal of Digestive Surgery

基　　金：江苏省卫生厅科技项目（H200770）;扬州市科技计划项目（YZ2008042）

摘　　要：目的检测低氧诱导因子仪（HIF-1α）在自体原位肝移植大鼠肝脏的表达情况，探讨HIF-lα在JNK信号转导通路中的作用机制。方法采用单纯随机抽样法将96只SD大鼠分为正常对照组、自体肝移植组、低氧预适应＋自体肝移植组，每组32只。正常对照组：仅开腹分离血管，不作其他处理；自体肝移植组：采用经门静脉灌注法建立稳定的70％自体原位肝移植模型；低氧预适应＋自体肝移植组：术前用8％氮氧混合气体低氧预处理90 min，其他处理同自体肝移植组。分别于术后1、2、12、24h检测大鼠血清ALT、AST水平，免疫组织化学染色法测定大鼠肝脏组织HIF-1α的表达，RT-PCR检测c-JunmRNA表达水平，Western blot检测Cleaved Caspase-3蛋白表达水平。多组比较采用方差分析，两组比较采用t检验。结果术后l、2、12、24h，低氧预适应＋自体肝移植组大鼠血清ALT和AST水平显著低于自体肝移植组，但高于正常对照组，差异有统计学意义（F=2631．371、1177．642、810．383、682．848，743．618、1095．522、375．995、580．613，P〈0．05）。自体肝移植组大鼠术后各时相点HIF-1α蛋白的表达水平明显低于低氧预适应＋自体肝移植组，但均高于正常对照组，差异有统计学意义（F=191．737，284．482，459．419，215．782，P〈0．05）。低氧预适应＋自体肝移植组大鼠术后1、2、12hc-Jun mRNA表达水平显著低于自体肝移植组，但均高于正常对照组，差异有统计学意义（F=66．211，53．169，9．645，P〈0．05），术后24hc-Jun mRNA表达水平3组间比较，差异无统计学意义（F=1．100，P〉0．05）。低氧预适应＋自体肝移植组大鼠术后各时相点Cleaved Caspase-3蛋白表达水平显著低于自体肝移植组，但均高于正常对照组，差异有统计学意义（F=23．133，31．158，14．547，29．043，P〈0．05）。结论肝移植大鼠低氧预适应后HIF-1α的�Objective To investigate the expression of hypoxia inducible factor-lα （HIF-let） in the transplanted liver in rats and the role of HIF-1α in the JNK signaling pathway. Methods Ninety-six SD rats were randomly divided into normal control （NC） group, autotransplantation （AT） group, hypoxia preconditioning （HP） ＋ AT group according to simple random sampling method. No treatment was applied to the rats in the NC group except for blood vessel separation. Stable rat models of 70% AT was established in the AT group. Rats in the HP ＋ AT group were given 8% oxygen mixed gas for 90 minutes before the operation. The levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected at 1, 2, 12, 24 hours after operation, and the expression of HIF-1α in the hepatic tissue, mRNA expression of c-Jun, and protein expression of Cleaved Caspase-3 were detected by immunohistochemical staining, reverse transcription-polvmerase chain reaction and Western blot, respectively. All data were analyzed using the analysis of variance or t test. Results The levels of ALT and AST in the HP ＋ AT group were significantly lower than those in the AT group, while higher than those in the NC group at 1, 2, 12 and 24 hours after the operation （F =2631. 371, 1177. 642, 810. 383, 682. 848; 743. 618, 1095. 522, 375. 995, 580. 613, P 〈0.05）. The protein expression levels of HIF-1α in the AT group were significantly lower than those in the HP ＋ AT group, but higher than those in the NC group at 1,2, 12 and 24 hours after operation （ F = 191. 737,284.482,459.419,213.782, P 〈0.05 ）. The mRNA expression levels of c-Jun in the HP ＋ AT group were significantly lower than those in the AT group, while higher than those in the NC group at 1, 2 and 12 hours after operation （F=66. 211, 53. 169, 9.645, P〈0.05）. There was no significant difference in the mRNA expression of c-Jun among the 3 groups at 24 hours after operation （ F = 1. 100, P 〉 0.05 ）. The protein expressions of Cle

关 键 词：肝移植 自体 低氧诱导因子α C-JUN氨基末端激酶 CASPASE-3 缺血再灌注损伤 

分 类 号：R657.3[医药卫生—外科学]