Effects of altitude hypoxia on cerebral blood distribution of sodium valproate in mice / 中国药理学通报

ABSTRACT

Aim To investigate the effects of altitude hypoxia on serum sodium valproate eoncentration and eerebral blood distribution.Methods Male mice were divided into control group and plateau group.Each group was given sodium valproate orally and intrave¬nously, respectively.UFLC-MS/MS was used to deter¬mine the concentration of sodium valproate in plasma and brain, and Western blot was used to detect the ex¬pression of P-gp in BBB.Results Compared with the control group, the ratio of brain/blood drug concentra¬tion in plateau group was up-regulated by 44.0% , 57.9% , 176.8% and 184.5% at 10, 30, 60 and 120 min, respectively.The ratio of brain/blood drug con-centration increased by 33.9% , 50.6% and 125.6% at 60 min, 120 min and 240 min in plateau group, re¬spectively.Compared with the control group, the ex¬pression of P-gp protein in BBB of mice in altitude group was significantly down-regulated by 58.46% (P < 0.05 ).Conclusions Compared with the control group, the brain/blood drug concentration ratio of val¬proic acid increases in high altitude hypoxia environ¬ment.Meanwhile, it is found that P-gp expression lev-el decreased in the brain mierovessels of mice under high altitude hypoxia environment, and the cerebral and blood distribution of valproic acid in mic increases in high altitude hypoxia environment.