Study on therapy strategy of recombinant human erythropoietin to promote angiogenesis after traumatic brain injury in rats

Abstract

Objective To research the effect and mechanism of phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase (Akt) and extracellular signal-regulated kinase (ERK1/2) signaling pathway in recombinant human erythropoietin to promote angiogenesis after traumatic brain injury in rats. Methods One hundred and twenty-five adult Sprague-Dawley rats were randomly divided into 5 groups including sham group (n=25), operation group (n=25), traumatic brain injury (TBI) group (n=25), recombinant human erythropoietin (rhEPO) + wortmannin group (n=25), rhEPO+ PD98059 group (n=25) and rhEPO treatment group (n=25). The TBI model was established by Feeney method. The expression of p-Akt、p-ERK1/2 and vascular endothelial growth factor A (VEGF-A) in the cerebral tissue were determined by Western blotting, and the microvessel density (MVD) was measured by immunohistochemistry. Results The density of microvessel in the cerebral tissue was higer in the rhEPO group [ (50.83±11.67) microvessels per 200×field] than the TBI group [ (14.67±3.98) microvessels per 200×field] (P=0.001) and the expression levels of p-Akt、p-ERK1/2 and VEGF-A were higer in the rhEPO group than the TBI group (P=0.036, 0.039, 0.025). The density of capillary in the cerebral tissue was lower in the rhEPO+ wortmannin group [ (22.33±3.88) microvessels per 200×field] than the rhEPO+ PD98059 group [ (40.50±8.83) microvessels per 200×field] (P=0.001) and the expression level of VEGF-A was lower in the rhEPO+ wortmannin group than the rhEPO+ PD98059 group (P=0.034). Conclusion rhEPO promote the expression of VEGF-A and angiogenesis through the PI3K/Akt and ERK1/2 pathways, and the PI3K/Akt pathway may play a more important role than ERK1/2. Key words: Traumatic brain injury; Angiogenesis; Recombinant human erthropoietin; Signal pathway