The Effects Of RhG-CSF On The Expression Of C-Jun N-termin-al Kinase And Extracellular Signal-regulated Kinase Following Focal Cerebral Ischemia/Reperfusion Injury In Rats

Objective:To investigate the effects of recombinant human granulocyte colony stimulating factor(rhG-CSF) on the expression of phosphorylated c-Jun N-terminal kinase、phosphorylated extraecellular signal-regulated kinase and cell apoptosis in rats with focal cerebral ischemia/reperfusion,to explore the anti-apoptosis mechanisms of rhG-CSF.Methods:Thirty six male Sprague-Dawley rats were randomly divided into the sham-operated group, the middle cerebral artery occlusion/reperfusion group (MCAO/R) and the rhG-CSF-treatment group, and12rats were included in each group. The middle cerebral artery occlusion reperfusion model was established by the suture method. The rhG-CSF-treatment group received a single dose of50μ/kg of rhG-CSF which were hypodermicly injected at the onset of reperfusion and24hours after the reperfusion. The sham-operated group and MCAO/R group received the same volume of saline. After48hours of reperfusion, rats were decapitated in all the groups. The expression of p-JNK and p-ERK were detected by immunohistochemical method and the apoptosis cells were tested by TUNEL method. The infarction volume was measured by TTC stain and the neurological function scores were assessed on Longa5Point scale.Results:1. The MCAO/R group and rhG-CSF-treatment group had different degrees of limb paralysis after cerebral ischemia reperfusion. Compared with the MCAO/R group, the neurological scores of the rhG-CSF-treatment group reduced and the mental state improved, significant statistical difference were found between the two groups (P<0.05).2.After TTC staining, the infarction was not found in the sham-operated group, While the right parietal cortex and striatum of cerebral infarction were seen clearly in the MCAO/R group and rhG-CSF-treatment group. But compared with the MCAO/R group, the volume of infarction reduced in the rhG-CSF-treatment group(P<0.05).3.Compared with the sham-operated group, the expression of p-JNK and p-ERK and TUNEL positive cells were increased in the MCAO/R group and rhG-CSF-treatment group(P<0.05). Compared with the MCAO/R group, the expression of p-JNK and TUNEL positive cells were diminished in the rhG-CSF-treatment group (P<0.05), while the expression of p-ERK was obviously increased.Conclusion:1. rhG-CSF can decrease neurological function scores and contribute to the recovery of limbs after the MCAO/R.2. The effects of rhG-CSF can reduce infarction volume after MCAO/R.3. rhG-CSF can inhibit the expression of p-JNK, enhance the expression of p-ERK and reduce TUNEL positive cells, which might be the mechanism of rhG-CSF neuroprotection.