高迁移率族蛋白B1参与心肺复苏术后大鼠海马组织P38MAPK信号通路的激活

HMGB1 involved in the activation of P38MAPK signaling pathway in the hippocampus of rats after cardiopulmonary resuscitation

目的探讨高迁移率族蛋白B1(HMGB1)在心肺复苏(CPR)术后大鼠海马组织激活P38 MAPK信号通路的作用。方法将SD大鼠随机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5个亚组)。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,干湿称重法测定脑组织含水量,RTPCR法检测HMGB1 mRNA表达,Western blot检测HMGB1和P38激酶活性。结果假手术组海马组织结构未见明显变化,复苏组存在缺血病理改变,24 h最为显著。与假手术组比较:复苏组脑组织含水量、海马HMGB1 mRNA表达均呈先上升后下降的趋势,于24 h达到峰值(P<0.01);复苏组HMGB1表达在ROSC后2 h显著降低,6和12 h逐渐增高,24 h达到峰值(P<0.01);复苏组海马组织P38激酶活性于2 h表达显著升高(P<0.01),6 h达到高峰(P<0.01),后缓慢下降。结论 HMGB1可能通过参与P38 MAPK信号通路的激活介导CPR术后早期脑组织炎性反应损伤。

Objective To investigate the role of HMGB1 involved in the activation of P38MAPK signal pathway in the hippocampus of rats after cardiopulmonary resuscitation. Methods Rats were randomly divided into two groups as shame-operated group, CPR group including 2, 6, 12, 24 and 48 h after restoration of spontaneous circulation （ROSC） （5sub-groups）. The animals were sacrificed and hippocampus were removed at the indicated time. Patholog- ical changes were examined at each time point. Calculated the brain water content by day/wet ration. The HMGB1 mRNA expression was detected by RT-PCR technique. The expressions of HMGB1 and P38MAPK activity were deter- mined using Western blot. Results There were no histopathological change in the hippocampus of rats in shame-op- erated group, brain tissue appeared change of ischemia pathology in CPR group, it was the most severest at ROSC 24 h. The brain water content, HMGB1 mRNA in rats of CPR 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 CPR significantly declined at 2 h after ROSC（P 〈0.01 ） and increased obviously at 6, 12 h and reached peak 24 h later（P 〈 0. 01 ）, the P38MAPK activity in the hippo- campus of rats after CPR, significantly increased at 2 h after ROSC and reached peak 6 h later（P 〈0.01 ） , then declined slowly later, much higher than that of shame-operated group. Conclusions HMGB1 involved in the acti- vation of P38 MAPK signal pathway may play an important role in the early stages of brain injury after CPR.