Expression Of Caspase-3、BNIP3in Cerebral Ischemia Reperfusion Rats’s Brain By Etanercept

Objective This study was designed to observe the changes of The Recombinant Human Tumor Necrosis Factor-a Receptor II:IgG Fc Fusion Protein for Injection (Etanercept) to neurologic deficit score, pathological neural behavior morphology, the expression of TNF-a/BNIP3/Caspase-3in cerebral cortex of cerebral ischemic model rats.To investigate the effects of Etanercept on cerebral ischemic-reperfusion injury and its echanism, supply experimental basis to the treatment of cerebral ischemic-reperfusion injury.Methods:Seventy-five rats were randomly divided into five groups: fifteen rats in sham group, fifteen rats in MCAO group, forty-five in different doses of Etanercept group(0.2mg/kg0.4mg/kg0.8mg/kg)).The rats were sacrificed at1d、2d、5d after model establishment.HE staining was used to observe the pathological structure changes. The expression of TNF-α、BNIP3、Caspase-3were observed by immunohistochemistry (IHC).The datas were analyzed with the help of statistical software SPSS17.0.Results1.The neurological function deficit of Etanercept group were lower than that of the model group(P<0.05). The difference between.the three groups(0.2mg/kg0.4mg/kg0.8mg/kg) is significant (p<0.05).2. Brain tissue pathomorphology:model group nerve cells are smaller in size, neuronal nuclear stain deepen, nucleolus shrinked, cribriform necrosis, The brain neurons of edema show in Etanercept group,but living nerve cells are more than model group.3. Immunohistochemistry results:(1) TNF-α、BNIP3、Caspase-3expression is reduced in Etanercept Group. There was significant difference at the same time between Etanercept Groups (P<0.05).(2) Caspase-3expression of every dose Etanercept group:There were significant differences between every dose groups (P<0.05) in the same time point.,except of the comparison between Etanercept group(0.2mg/kg) and Etanercept group(0.4mg/kg) at5d.(3) TNF-α、BNIP3expression of Etanercept groups:There were significant differences between every dose groups (P<0.05) at the same time.Conclusion1. Etanercept can protect the brain cerebral ischemia reperfusion injury and the effects were dose-related.2. Etanercept reduces the levels of Caspase-3in Caspase dependant pathway, so as to inhibit the neural apoptosis. Etanercept may suppress BNIP3expression in the Caspase independant pathway.