The activation of extracellular regulated protein kinase 1/2 induces neuron autophagy in the hippocampous in a rat model of subarachnoid hemorrhage / 中国神经精神疾病杂志

ABSTRACT

Objective To investigate the relationship of extracellular regulated protein kinases activation and neural cells autophagy in rats after subarachnoid hemorrhage.Methods One hundred twenty male SD rats were randomly divided into sham operated group,SAH group,ERK1/2 inhibitor U0126 group,autophagy inducer rapamycin (Rap) group.The animal models were established by injecting the autologous blood into cisterna magna twice.U0126 (5μ g/μL) and Rap (10nmol/μL) were injected into lateral ventricles in U0126 group and Rap group 30min before SAH.The morphology of hippocampal nerve cells were examined by using light microscopy.The expression levels of phosphorylated ERK 1/2 (p-ERK 1/2),ERK 1/2mRNA and autophagy markers (Beclin-1 and Beclin-1 mRNA、LC3-Ⅱ and LC3mRNA) in the hippocampus were detected by using inmunohistochemistry and real-time fluorescence quantitative PCR.Result Compared with sham group,the rate of dead nerve cells,the mRNA levels of ERK1/2,Beclin-1 and LC3 as well as the levels of the p-ERK1/2,Beclin-1 and LC3-Ⅱ increased in SAH group (P＜0.05).Compared with SAH group,the rate of dead nerve cells increased(P＜0.05),the ERK1/2 mRNA,Beclin-1 mRNA and LC3 mRN A,and p-ERK1/2,Beclin-landLC3-Ⅱ in U0126 group decreased(P＜0.05);the rate of dead nerve cells decreased (P＜0.05),the Beclin-1 mRNA and LC3 mRNA,the Beclin-1and LC3-Ⅱ level increased in Rap group(P＜0.05),but ERK 1/2 mRNA and p-ERK 1/2 remained unchanged (P＞0.05).Conclusion Activation of the ERK1/2 signaling pathway after SAH,can induce nerve cells death by increasing Beclin-1 and LC3-Ⅱ expressions.