The Upregulation Effect Of Neureglin On ERK5 Signaling Pathway In Rats With Cerebral Ischemia Reperfusion Injury

Objective: The aim of this study is to explore the regulating mechanism of neureglin on ERK5 signaling pathway in rats with cerebral ischemia reperfusion injury.Methods: A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion(MCAO),and the rats were divided randomly into sham operation group,control group,treatment group,inhibitor group,and inhibitor combined treatment group.The rats were treated by injecting 5?l(2?g/kg)NRG1? from internal carotid artery.This inhibitor BIX02189 were injecting in the brain of rats before ischemiafrom internal carotid artery.The laser Doppler regional cerebral blood flow detector was used to evaluate the success of cerebral ischemia-reperfusion model.The neurobehavioral functions were evaluated by the modified neurological severity score(m NSS)test.The apoptotic cells were counted by terminal deoxynucleotidyl transferase d UTP nick-end labeling,and the expressions of phosphorylated MEK5,ERK5 and MEF2 C were determined by immunohistochemical assay and Western blot.The ultrastructure of neuron,myelin sheath and blood brain barrier were detected by transmission electron microscope.Results: After cerebral ischemia,the rCBF of rats significantly dropped to no more than30% of the r CBF at before insertion of line plug,while after reperfusion,the r CBF returned to more than 80% bebofe insertion of line plug.In model group,the damage of cortex infarctions,nerve cells and neurons structure was aggravating,the number of apoptotic cells increased,and the expression of p ERK5 protein compensatorily enhanced after cerebral ischemia reperfusion injury.Compared with the model group,the expression of p ERK5 protein further enhanced(P<0.001),the damage of nerve cells alleviated(P<0.01),the apoptotic cells significantly decreased(P<0.05),neurobehavioral functions were significantly improved(P<0.001),the ultrastructure of neuron,myelin sheath and blood brain barrier weresignificantly improved in the treatment group.In the inhibitor group,cortex nerve cell seriously damaged,the number of apoptotic cells obviously increased,the expression of p ERK5 protein significantly decreased,and the neurobehavioral functions seriously damaged,the ultrastructure of neuron,myelin sheath and blood brain barrier wereseriously damaged.Compared with the inhibitor group,the expression of p ERK5 protein inthe inhibitor plus treatment group obviously increased(P<0.01),the nerve cell seriously damaged,the volume of cerebral infarction significantly reduced,the number of apoptotic cells obviouslyreduced(P<0.001),the ultrastructure of neuron,myelin sheath and blood brain barrier weresignificantly improved.Conclusion: The results suggested that NRG1? could play a neuroprotective role by activating the MEK5-ERK5-MEF2 C signaling pathway and up-regulate further expressions of p MEK5,p ERK5 and p MEF2 C to inhibit the inflammation induced by cerebral ischemia reperfusion injury in rats.