弥漫性脑创伤大鼠海马区Homer1a表达与p38MAPK激活的关系

Relationship between Homer1a Expression and p38MAPK Phosphorylation in Hippocampus after Diffuse Brain Injury in Rats

目的探讨弥漫性脑创伤(DBI)大鼠海马区Homer1a表达与p38有丝分裂原活化蛋白激酶(MAPK)的关系。方法将雄性SD大鼠149只分为对照组、轻度DBI组、重度DBI组。参照Marmarou′s法制作大鼠DBI模型。应用光镜和电镜观察脑组织形态变化;免疫组化及Western blot法检测海马区Homer1a和磷酸化p38MAPK表达。结果重度DBI组大鼠死亡率(49.3%)明显高于轻度DBI组(22.2%)(P<0.05)。电镜下,重度DBI组中神经元内细胞器、轴索及毛细血管等超微结构的损伤程度明显高于轻度DBI组。与对照组比较,2组DBI组1、6、24、48、72 h Homer1a和磷酸化p38MAPK表达均增高(P<0.05),轻度DBI组中Homer1a和磷酸化p38MAPK 24 h达高峰,48 h和72 h下降,但仍明显高于对照组(P<0.05);重度DBI组中Homer1a表达在6 h出现峰值,高表达持续至24 h;磷酸化p38MAPK 24 h达高峰。重度DBI组中1 h、6 h和24 h Homer1a表达高于轻度DBI组,48 h和72 h低于轻度DBI组(P<0.05);各时间点磷酸化p38MAPK表达均高于轻度DBI组(P<0.05)。相关分析显示轻度DBI组Homer1a与磷酸化p38MAPK表达相关(r=0.942,P<0.05);重度DBI组Homer1a与磷酸化p38MAPK表达相关(r=0.896,P<0.05)。结论 DBI大鼠海马区Homer1a表达与p38MAPK激活有关。

Objective To investigate the relationship between Homerla and p38MAPK phosphorylation in hippocampns after severe diffuse brain injury in rats. Methods 149 male Sprague-Dawley rots were divided into three groups ： control group, mild DBI group and severe DBI group. DBI rat model was established according to the description of Marmarou＇ s diffused brain injury. The histopathologic changes of hippocampns were ob- served by light and electron microscope. The expressions of Homerla and phosphorylated p38MAPK were observed by immtmohistochemistry and Western blot. Restflts The rate of death rats in severe DBI group （49.3%） was higher significantly than that in mild DBI group （ 22.2% ） （ P 〈 0.05 ）. The damaged degree of ultrastructure including organelle, axonal and capillary in mild DBI group was higher significantly than that in severe DBI group under the electron microscope. The expressions of Homerla and phosphorylated p38MAPK increased at each time points in the two DBI groups when compared with control group （P〈 0.05） ; Homerla reached the peak at 24 h and decreased at 48 h and 72 h in mild DBI group and it reached the peak at 6 h and continued to 24 h and decreased at 48 h and 72 h in severe DBI group. Phosphorylated p38MAPK reached the peak at 24 h and decreased at 48 h and 72 h in mild DBI group and it also reached the peak at 24 h in severe DBI group. The expression of Homerla in se- vere DBI group was higher than that in mild DBI group at 1 h, 6 h and 24 h, while lower at 48 h and 72 h （P 〈 0.05 ）. The expression of phosphorylat- ed p38MAPK was higher at each time points in severe DBI group than that in mild DBI group（P〈 0.05）. Conclusion The dynamic expression of Homerla is related to p38MAPK phosphorylation in hippocampus after diffuse brain injury in rats.