Neuroprotective Effect Of RhEPO On Intracerebral Hemorrhage And Its Mechanism

Background:With the acceleration of the aging population,cerebrovascular disease,especially cerebral hemorrhage,has become a common serious disease that endangers human health.The disease has features:acute onset,rapid progress,high morbidity,high mortality and complicated Disease and so on,so far,the treatment of the disease is limited,the incidence of late complications is still high.But through scientific research on its pathogenesis and treatment,some progress were made.Erythropoietin(erythropoietin,EPO)is a hormone-like substance secreted by the liver and kidneys,used to regulate the generation of blood cells.Neuroprotective effect is the theoretical basis for the treatment of cerebrovascular disease,many experimental studies have shown,EPO could improve neurological function in patients with ischemic stroke,but the effect of EPO on the cerebral hemorrhage and the specific mechanism were not very clear.Our study is to explore whether the recombinant human erythropoietin(rhEPO)has neurological protection after cerebral hemorrhage with and its corresponding mechanism.Methods:30 Wistar male rats of 8 weeks old were randomly divided into 3 groups:sham group?ICH group and rhEPO group,The rats in the cerebral hemorrhage group were treated with ICH.In the sham operation group,the treatment were same as ICH group except blood injection.The rhEPO group was injected with rhEPO at 5min after operation.All animals were scored with neurological score.The rats were sacrificed 24 hours after the ICH model was established.The effect of neuronal apoptosis were detected by TUNEL staining.The expression of apoptosis protein Caspase3 was detected by immunehistochemical,and Real-time PCR and Western blot measured JAK2 and STAT5 mRNA expression and protein levels.Results:Neurological score was performed 24 hours after the establishment of the intracerebral hemorrhage model.According to the criteria of Longa5 standard,in ICH group,four rats were evaluated as score 1,three rats were rated as score 2 and two rats were rated as score 3.In rhEPO group,five rats were evaluated as score 1 and two rats were rated as score 2,one rats were rated at score 3,indicating that rhEPO can ameliorate neuronal damage and restore nerve function after intracerebral hemorrhage in rats.Compared to sham group,the quantity of apoptotic cells and the expression of Caspase3 in ICH model group and rhEPO group were significantly increased(P<0.05);while the apoptotic cells in rhEPO group were significantly down-regulation compared with the ICH group(P<0.05).Compared with the sham group,the protein expression and mRNA expression of JAK2 and STAT5 in ICH group and rhEPO group were significantlyup-regulated(P<0.05);while the protein expression and mRNA expression of JAK2 and STAT5 in rhEPO group were decreased significantly compared to ICH group(P<0.05).Conclusion:rhEPO could reduce neuronal apoptosis by regulating JAK2 / STAT5 signal after cerebral hemorrhage,and has protective effect on the nervous system in rats.