高海拔地区大鼠严重烫伤延迟复苏后肝脏低氧诱导因子-1α和p53的表达与肝脏损伤的关系  

Influence of hypoxia inducible factor-1αand p53 expression on liver injury after severe scald with delayed fluid resuscitation in rats in high altitude

作　　者：刘毅[1] 张诚[1] 刘长海[1] 

机构地区：[1]兰州军区兰州总医院全军烧伤整形外科中心,甘肃兰州730050

出　　处：《兰州大学学报（医学版）》2011年第1期15-20,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：全军医学科技研究"十一五"计划课题(06G030)

摘　　要：目的探讨高海拔地区大鼠严重烫伤延迟复苏后肝脏低氧诱导因子-1α(HIF-1α)和p53的表达与肝脏损伤的关系。方法 Wistar大鼠240只,在1517和3848m两个海拔高度随机分为即时复苏(IFR)组、延迟复苏(DFR)组和假烫伤(SS)组,建立总体表面积30%的Ⅲ°烫伤模型,于伤后1、6、12、24、72和168h取材。采用组织病理学、组织芯片技术、脱氧核糖核苷酸末端转移酶介导的缺口末端标记(原位末端缺口标记)法、免疫组织化学染色与图像分析技术,观察肝组织病理学改变与细胞凋亡、HIF-1α和p53的表达。结果两个海拔高度实验组HIF-1α及p53蛋白表达强度均高于相对应的假烫伤组,随海拔梯度上升,HIF-1α及p53蛋白的表达均增强,各海拔高度DFR组高于IFR组(P<0.05);DFR组肝细胞凋亡率高于IFR组,且高海拔地区高于低海拔地区(P<0.05)。结论 HIF-1α蛋白积聚及p53促凋亡途径的激活,在高海拔地区严重烫伤延迟复苏肝损伤中可能发挥重要作用。Objective To explore the influence of hypoxia-inducible factor-1α （HIF-1α） and p53 expression on liver injury after severe scald with delayed resuscitation in high altitude in rats. Methods 240 Wistar rats were employed as the experimental models （TBSA 30%, III degree）, and they were randomly divided into 3 groups in different altitudes （1 517 m and 3848 m）： delayed fluid resuscitation （DFR） group, immediate fluid resuscitation （IFR） group and sham scald （SS） group. The livers of rats were harvested at 1, 6, 12, 24, 72 hours and 168 hours after severe scald respectively. The levels of HIF-1α, p53 and the apoptosis percentage in liver were detected by pathological technique, tissue microarray technique, terminal deoxynucleotidy transferase- mediated deoxy-uridine triphosphate nick end labeling, immunohistochemistry and image analysis technique. Results The expression levels of HIF-1α and p53 were much higher in DFR group and IFR group than those in SS group, in 3 848 m altitude and in 1 517 m altitude, and higher in DFR group than those in IFR group （P 〈0.05）. The apoptosis percentage in liver was higher in DFR group than in IFR group, and higher in 3 848 m altitude than in 1 517 m altitude （P 〈0.05）. Conclusion HIF-1α expression and activation of p53 apoptotic pathways may play an important role in the hypoxic injury of the liver.

关 键 词：高海拔 大鼠 烫伤 延迟复苏 肝脏 低氧诱导因子1Α p53蛋白 

分 类 号：R644[医药卫生—外科学]