Effects of recombinant human erythropoietin on learning and memory abilities and expressions of P53 and Bcl-2 proteins in rats induced by chronic cerebral ischemia

Abstract

Objective To study the effects of recombinant human erythropoietin (rhEPO) on learning and memory functions and expressions of apoptosis-related proteins (P53 and Bcl-2) in rats induced by chronic cerebral ischemia.Methods Sixteen healthy male SD rats were randomly divided into control group and experimental group (n=8); the permanent bilateral occlusion of common carotid arteries in these rats was adopted to establish the chronic cerebral ischemia models; rats in the experimental group weekly received intranasal rhEPO delivery at the dose of 150 U/125 μL after chronic ischemia for 3 days,whereas models in the control group accepted equivalent volume of saline at the same time.Eight weeks after the inducement,Morris water maze test was performed to evaluate the movement and the spatial learning and memory capabilities.Morphology changes of cerebral cortex and hippocampal CA1 nerve cells were observed by HE staining.P53 and Bcl-2 proteins levels were detected by immunohistochemistry.The number of apoptotic cells was detected by means of TUNEL.Results Morris water maze test showed that shorter escape latency and higher frequency through platform in the experimental group were noted as compared with those in the control group (P＜0.05).HE staining indicated that less pyramidal cells and more serious karyopyknosis changes of cerebral cortex and hippocampal CA1 nerve cells and thinner cerebral cortex in control group were noted as compared with those in the experimental group (P＜0.05).Immunohistochemistry indicated that the experiment group had increased Bal-2 expression and mean gray value of P53 as compared with control group (P＜0.05).TUNEL showed that the apoptotic cells of control group were significantly increased as compared with those in the experimental group (P＜0.05).Conclusion The rhEPO can improve the abilities of movement,memory and spatial orientation in rats induced by chronic cerebral ischemia,whose mechanism might be related to the restrain apoptosis. Key words: Erythropoietin; Chronic cerebral ischemia; Intranasal delivery; Spatial learning and memory; Bcl-2; P53