Phosphorylation of signal transducer and activator of transcription-3 participate in neuroprotective effect of κ-opioid receptor after total cerebral ischemia/reperfusion in rats

Objective To investigate the role of signal transduction and activator of transcription-3(STAT3) phosphorylation in neuroprotection induced by κ-opioid receptor after total cerebral ischemia/reperfusion in hippocampus of rats.Methods Sixty male Sprague-Dawley rats were randomly divided into 5 groups(n=12):sham group(group A),ischemia/reperfusion group(group B),BRL52537(κ-opioid receptor agonist) +sham group(group C),BRL52537+ischemia/reperfusion group(group D),and nor-BNI(nor-binaltorphimine,κ-opioid receptor antagonist)+ischemia/reperfusion group(group E).Total cerebral ischemia was induced by four-vessel occlusion for 10 min in this study.Rats were treated with intravenous 1 mg/kg per hour BRL52537,initiated 15 min before occlusion and maintained until 4 hours of reperfusion.Before total cerebral ischemia,nor-BNI(25 μg) was given by intracerebroventricular injection.Six rats in each group were killed 24 h after modeling,and the expression of STAT3 and phosphorylated STAT3(p-STAT3) in the hippocampus were assessed by immunoblotting.The rest rats were killed 72 h after reperfusion,and neuropathological changes in hippocampus CA1 area were observed by Hematoxylin-Eosin(H-E) staining.Results No statistical differences in total STAT3 concentrations were found among groups(P0.05),and neither were there significant differences in p-STAT3 levels and the number of normal neurons in hippocampal CA1 area between group A and group C(P0.05).Compared with group A,the expression level of p-STAT3 was significantly increased in group B,D and E(P0.05).While compared with group B,the expression of p-STAT3 was remarkably increased in group D(P0.05),and remarkably decreased in group E(P0.05).Normal neurons in hippocampal CA1 area in group B,D and E were significantly less than those in group A(P0.05).Compared with group B,normal neurons in hippocampal CA1 area was remarkably increased in group D,and remarkably decreased in group E(P0.05).Conclusion p-STAT3 takes part in the neuroprotective effect of κ-opioid receptor after total cerebral ischemia/reperfusion in rats.