缺血预处理对大鼠减体积肝移植术后Akt生存信号通路的影响及其意义  

Effects of ischemic preconditioning on Akt survival signal pathway after reduced-size rat liver transplantation

作　　者：宋军[1] 徐为[1] 符炜[1] 华志元[2] 姚爱华[2] 俞悦[2] 李向农[1] 王学浩[2] 

机构地区：[1]徐州医学院附属医院普外科,江苏221002 [2]南京医科大学第一附属医院肝脏移植中心

出　　处：《中华实验外科杂志》2009年第11期1459-1460,共2页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（30671992）

摘　　要：目的探讨缺血预处理（IPC）对大鼠减体积肝移植术后Akt生存信号通路的影响及意义。方法将36只成年雄性SD大鼠随机分为2组：50％减体积肝移植组（Control组）和IPC组，Western blot检测肝组织总Akt和p-Akt及其下游的p-Bad和p-GSK3β蛋白水平，同时结合血清学和组织病理学分析Akt生存信号通路变化的意义。结果与Control组比较，IPC组术后6、24h丙氨酸转氨酶（ALT）水平显著下降（6h：1064．49±126．53比802．90±82．39；24h：1401．13±172．73比943．80±116．25，P〈0．01）；Control组术后24h，肝细胞明显空泡样变性伴局部坏死，小叶结构破坏，门脉周围水肿、充血，炎症细胞浸润明显，而IPC组损伤减轻；Western blot结果显示：与Control组比较，IPC组术后2、6、24h肝组织中p-Akt、p-Bad、P—GSK3β蛋白水平上调。结论IPC明显减轻减体积肝移植术后再灌注损伤，其机制可能与激活Akt生存信号通道密切相关。Objective To investigate the effect of ischemic preconditioning （IPC） on Akt survival signal pathways in rat reduced-size liver graft and its significance. Methods Thirty-six adult male SD rats were randomly divided into two groups ：50% sized liver transplantation group （control group） and IPC group. The expression of protein of Akt signaling pathway including total and phospho-Akt, phospho-Bad and phospho-GSK3β was assessed by Western blot. The change and significance of Akt survival signaling pathway was analyzed in rat reduced-size liver graft in combination with hepatic function and histopathological analysis. Results Compared with control group, serum ALT levels were significantly lower at 6th and 24th h after reperfusion in IPC group （ 6 h ： 1064.49 ± 126.53 vs 802.90 ± 82.39,24 h ： 1401.13 ± 172.73 vs 943.80 ± 116.25 P 〈0. 01 ）. Histopathological analysis showed disruption of lobular architecture, apparent hepatocelluar degeneration accompanied by focal necrosis; significant edema,congestion and inflammatory cell infiltration in periportal area at the 24th h after reperfusion in control group, whereas minimal damage was observed in IPC group. Western blot revealed that p-Akt,p-Bad and p-GSK3β expression levels were significantly up-regulated at the 2nd, 6th, and 24th h after reperfusion in IPC group compared to control group. Conclusion IPC could ameliorate early reperfusion injury in redueed-siz liver grafts, and the protective mechanisms might be mediated in part by activation of Akt survival signal pathway.

关 键 词：肝移植 再灌注损伤 缺血预处理 AKT信号通路 

分 类 号：R657.3[医药卫生—外科学] R542.2[医药卫生—临床医学]