[Effects of recombinant human erythropoietin on brain-derived neurotrophic factor expression in different brain regions of aging rats].

OBJECTIVE: To explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats. METHODS: Forty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments. RESULTS: Significant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region. CONCLUSION: Treatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.

[The anti-aging effect of EPO and the preliminary probe into its mechanisms].

OBJECTIVE: To study whether erythropoietin ( EPO) has the anti-aging effect and the mechanisms of how it effects. METHODS: 5% D-galactose hypodermic injection for 6 weeks to establish the aging model. Divided rats into 5 groups randomly: the normal control (group A), the aging model (group B), the low dosage (1 000 U/ (kg x d)) of recombinant human erythropoietin (rhEPO) intervene (group C), the middle dosage (3 000 U/(kg x d)) of rhEPO intervene (group D) and the high dosage (5 000 U/(kg x d)) of rhEPO intervene (group E), 10 rats in each group. Morris water maze was used to comparing the behavioral indexes. After decapitating the rats, the malonaldehyde (MDA), Na(+)-K+ ATPase, total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) of brain tissue were tested. One rat from each group was selected randomly to observe the hippocampal ultramicrostructure. RESULTS: (1) Compared with group A, the learning and memory ability of group B reduced, the level of MDA, the Na(+)-K+ ATPase, T-AOC and the SOD activities of brain tissue decreased (P < 0.05), besides, a series of aging changes were observed in the hippocampal ultramicro-structure in group B. (2) Compared with group B, an improved learning and memory ability of group D, a reduced MDA content and an increased activity of Na(+)-K+ ATPase, T-AOC and the SOD activities of brain tissue in group D were also observed with a improved hippocampal ultramicro-structure. (3) The low dosage of rhEPO intervention could against the decrease of the activities of brain Na(+)-K+ ATPase, SOD of aging rat (P < 0.05), but had no significant effects on the rest of the indicators. The high dosage of rhEPO intervention had no significant improvements on various indicators of aging rats in high dosage of rhEPO intervention group was noticed (P > 0.05). CONCLUSION: The middle dosage of EPO has the anti-aging effect, and its mechanisms may be related to enhancing the antioxidant enzymes activity and increasing the antioxidant capacity.