The decline of EPO in brain of aging rats induced by d-galactose effect and the reverse of the water extract of radix rehmanniae preparata / 中国药学杂志

ABSTRACT

OBJECTIVE: To observe the change of EPO in brain of aging rat induced by D-galactose (D-gal) and the EPO-based antiaging of the water extract of Radix Rehmanniae Preparata (WERRP). METHODS: D-gal-treated groups were received subcutaneous injection of D-gal at dose of 50, 150 and 250 mg·kg-1 daily for 8 weeks to imitate an aging model that was induced by oxidative stress. After the detection of EPO in hippocampus, the 150 mgaging model. In addition the WERRP-treated group and vehicle group was set. The WERRP-treated group was given WERRP oral gavage at a dose of 4 gMorris water maze (MWM) test was used to assess the spatial learning and memory. SOD, MDA and β-galactosidase in brain were examined by Assay Kits. Finally, EPO, EPOR, and HIF-2α in hippocampus were determined by immunohistochemistry and Western blot.

RESULTS:

D-gal-treated group showed significant longer latency to platform and less times of cross the platform (P < 0.05) in MWM. After treated with D-gal, SOD was drastically decreased and MDA and β-galactosidase were remarkably increased in brains compared with vehicle (0.9% saline), treated rats (P < 0.01). In addition, the expression of EPO, EPOR and HIF-2α were significantly decreased in the brains of D-gal-treated rats compared with vehicle-treated rats. Meanwhile, there was a negative correlation between EPOR and MDA in content. Interestingly, WERRP-treated rats showed significant improvement of spatial learning and memory, decrease of oxidative stress and enhancement of EPO/EPOR in the brain compared with 150 mg < kg-1 D-gal-treated rat (P < 0.05).

CONCLUSION:

The aging rats induced by D-gal show a significant decline of EPO in brain which indicate the decrease of brain EPO in aging is related to the increase of oxidative stress. That WERRP reverses the decline of the EPO expression in aging model may be the underlying mechanism of the role of anti-aging of WERRP.