Effects of MAPK activation on autophagy in the hippocampus of rats with subarachnoid hemorrhage / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effect of MAPK activation on autophagy in the hippocampus of rats with subarachnoid hemorrhage.Methods A total of 100 male SD rats were divided into 5 groups randomlysham operated group,SAH group,inhibitor U0126 group,inhibitor SB203580 group,SP600125 group.The animal model was established by injecting the autologous blood into cisterna magna twice.The morphological changes of hippocampus nerve cells of rat brain were detected with HE.The mRNA levels of ERK1/2,p38MAPK,JNK and LC3 in hippocampus were detected with quantitative real time PCR and the expression of phosphorylated ERK1/2,phosphorylated p38MAPK,phosphorylated JNK and LC3-Ⅱ in hippocampus of rat brain were detected by immunohistochemistry.Results Compared with the Sham group,the survival rate of neurons in SAH group decreased (6 h(84.982 ± 5.723) ％,24 h(74.383± 9.860) ％,48 h(62.860± 10.820) ％,72 h(52.260± 10.960) ％) (all P＜0.05).The levels of ERK1/2 mRNA,p38MAPK mRNA,JNK mRNA and LC3 mRNA in hippocampus increased (all P＜ 0.05) and the expression of p-ERK1/2,p-p38MAPK,p-JNK,LC3-Ⅱ proteins increased(all P＜0.05).Compared with the SAH group,the survival rate of neurons in U0126 group was decreased (6 h(71.620±6.542) ％,24 h(66.221±7.742)％,48 h(55.208±8.802) ％,72 h(46.242±7.782) ％),and the ERK1/2 and LC3 in hippocampus decreased both in mRNA level and in protein level(all P＜0.05).Compared with the SAH group,the survival rate of neurons in SB203580 groups was increased (6 h(89.082±6.602)％,24 h(85.840±9.726) ％,48 h(74.96± 10.916) ％,72 h(69.211 ± 10.745) ％),and the p38MAPK,LC3-Ⅱ in hippocampus decreased at both mRNA and protein levels (all P＜0.05).Compared with the SAH group,the survival rate of neurons in SP600125 groups was increased (6 h(91.620± 7.542) ％,24 h(86.221 ± 10.742) ％,48 h(75.208±11.802) ％,72 h(70.242± 11.782) ％).The expression of JNK was decreased while the LC3-Ⅱ was increased in hippocampus (P＜0.05).Conclusion MAPK activation is involved in the autophagy of hippocampal neurons after SAH,in which ERK1/2 activation plays a positive role in the regulation of autophagy in hippocampal neurons after SAH,while p38MAPK and JNK activation plays a negative role in autophagy.