心肺复苏术后大鼠海马组织高迁移率族蛋白B1和NF-κB的表达及相关性分析

摘要

Objective To observe the changes of high mobility group box 1(HMGB1) and nuclear factorκB(NF‐κB) expres‐sion in the hippocampus of rats after cardiopulmonary resuscitation so as to unravel the role of HMGB 1 and NF‐κB in neuroin flam‐mation .Methods Totally 40 Sprague‐Dawley rats were randomly divided into shame‐operated group and recover group [including 2 ,6 ,12 ,24 and 48 h of 5sub‐groups after restoration of spontaneous circulation (ROSC)] .The animals were sacrificed and hippo‐campus were removed at the indicated time .Pathological changes were observed at each time point .The expression of HMGB1 and NF‐κB were determined using RT‐PCR and Western blot respectively .Results There were no histopathological in the hippocampus of rats in shame‐operated group ,brain tissue appeared change of ischemia pathology in recover group ,it was the most severest at ROSC 24 h and still obviously at ROSC 48 h time point .HMGB1 mRNA and NF‐κB mRNA expression in the hippocampus of rats of recover group increased obviously along with the prolongation of time following ROSC and reached its peak at ROSC 24 h(P<0 . 01) ,much higher than that of shame‐operated group ;the HMGB1 level in the hippocampus of rats after recover significantly de‐clined at 2 h after ROSC and increased obviously at 6 ,12 h and reached peak 24 h later ,then decreased 48 h later(P<0 .01) ,there was positive correlation between the expression of HMGB1 and NF‐κB protein .Conclusion HMGB1/NF‐κB signaling pathway may play an important role in the early stages of brain injury after cardiopulmonary resuscitation .Targeted therapies of this path way would be possible to open a new avenue for preventing neuroinflammation after recover .%目的：观察高迁移率族蛋白B1（HMGB1）、核转录因子（NF‐κB）在心肺复苏术后大鼠海马组织内的表达，以期探讨其可能意义。方法40只SD大鼠分为假手术组和复苏组（按复苏后自主循环恢复后2、6、12、24和48 h各时间点分为5亚组）。在相应的时间点断头处死，取海马组织，HE染色观察海马病理变化，RT‐PCR和Western Blot检测HMGB1、NF‐κB水平表达，并对二者进行相关分析。结果病理切片显示假手术组海马结构未见明显变化，复苏组存在缺血病理改变，24 h最为显著，48 h损伤仍比较重；与假手术组比较，复苏组海马HMGB1、NF‐κB mRNA表达均呈先上升后下降的趋势，均于24 h达峰值（P＜0．01）；复苏组HMGB1蛋白表达在自主循环恢复后2 h显著降低，24 h达到峰值，在48 h稍下降，差异均有统计学意义（P＜0．01）；HMGB1和NF‐κB蛋白表达呈显著正相关。结论 HMGB1／NF‐κB信号通路可能参与心肺复苏术后早期脑炎性损伤，干预此通路的靶向性治疗有望减轻心肺复苏术后脑炎性损伤。