Mechanism Of Recombinant Human Erythropoietin Promoting Angiogenesis Following Earlytraumatic Brain Injury In Rats

Objective To investigate the role of recombinant human erythropoietin(rhEPO)promoting angiogenesis in early traumatic brain injury of rat through the phosphatidylinositol 3-hydroxy kinase(PI3K)/ protein kinase B(Akt) and extracellular signal regulated kinase 1/2 pathway.Method 150 Male SD rats were divided into five groups : Sham group(n=30),traumatic brain injury group(TBI group, n = 30), TBI treated with wortmannin group(n=30), TBI treated with PD98059 group(n=30) and TBI treated with rhEPO group(n=30). Feeney’s method was applied to establish TBI model. Expression of p-Akt/p-ERK1/2/VEGF-A were observed by Western blot analysis. Micro vessel density(MVD)was detected by Immunohistochemistry.Results At the time point of 1day, 2day, 3day, 5day, 7day after modeling, expression of p-Akt、p-ERK1/2、VEGF-A have been significantly(p< 0.05) enhanced in TBI treated with rhEPO group compared with traumatic brain injury group; expression of VEGF-A have been significantly(p< 0.05) reduced in TBI treated with wortmannin group compared with TBI treated with PD98059 group. On 14 day after modeling, MVD counts of brain injury tissue have been significantly(p< 0.05) enhanced in TBI treated with rhEPO group(50.83±11.67/200 times the vision) compared with traumatic brain injury group(14.67±3.98/200 times the vision). MVD counts of brain injury tissue have been significantly(p<0.05) reduced in TBI treated with wortmannin group(22.33±3.88/200 times the vision) compared with TBI treated with PD98059 group(40.50±8.83/200 times the vision).Conclusion PI3K/Akt and ERK1/2 pathway play an important role in expression of VEGF-A after rhEPO and in angiogenesis, and PI3K/Akt plays a bigger role than ERK1/2.