Effect of P38MAPK pathway on autophagy in rat hippocampus following cerebral ischemic postcoditioning / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the mechanism of ischemic postconditioning in relieving cerebral ischemia reperfusion (IR) by regulating autophagy through P38MAPK pathway.Methods Cerebral ischemia reperfusion model was established by using modified Pulsinelli four-vessel occlusion (4-VO).Totally 128 male SD rats were divided into 4 groups randomlycontrol group (sham),cerebral ischemia reperfusion model group (CIR),cerebral ischemic postconditioning group (CIP),and cerebral ischemic postconditioning + P38MAPK inhibitor group (SB203580 group).Each group was subdivided into four time points6 h,24 h,48 h,and 72 h.The morphological changes of the hippocampus CA1 area neurons at each time point and the number of surviving nerve cells were detected with HE staining.The expression of the hippocampus CA1 area phosphorylated P38MAPK and the autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with immunohistochemistry.The protein content of the hippocampus phosphorylated P38MAPK and autophagy-related genes of Beclin-1 and LC3-Ⅱ were detected with Western blotting.Results Compared with those in sham group,the damage of rats' hippocampal neuron structure and the survival rate of neurons at each time point decreased in CIR group,the expressions of p-P38MAPK,LC3-Ⅱ and Beclin-1 increased.Compared with those in CIR group,in CIP and SB203580 groups the structure of rats hippocampal neurons was improved,the survival rate of neurons increased,the expression of p-P38MAPK decreased and the expressions of LC3-Ⅱ and Beclin-1 increased at each time point.Compared with CIP group,SB203580 grouphad improved structure of rats' hippocampal neurons,increased survival rate of neurons,decreased expression of p-P38MAPK,and increased expressions of LC3-Ⅱ and Beclin-1 at each time point.Conclusion Cerebral ischemic postconditioning through inhibiting P38MAPK pathway can regulate autophagy and exert its nerve-protective effect.