The protective effect of fluoxetine hydrochloride on brain tissues of rats with high altitude cerebral edema / 中国药理学通报

ABSTRACT

Aim To study the protective effect of fluoxetine hydrochloride on brain tissues of rats with simulated high altitude cerebral edema(HACE)and its mechanism.Methods The optimal dosage and time of fluoxetine hydrochloride were determined by the hypoxia tolerance test of mice under normal pressure.The rat model of brain edema at high altitude was established by large-scale low-pressure oxygen chamber.HE staining was used to observe the pathological changes of brain tissues in rats.Microplate reader was used to detect the corresponding indexes of oxidative stress such as malondialdehyde(MDA)level and superoxide dismutase(SOD)activity.The expressions of hypoxia-related proteins HIF-1α,VEGF,MMP-9,AQP4 and SERT were detected by Western blot.Results Compared with the hypoxia model group,after the intervention of fluoxetine hydrochloride,the survival time of mice was prolonged,and the middle dose of fluoxetine(14 mg·kg-1)had the best effect,with an extension rate of 17.78%.The pathological damage of brain was improved,the water content of brain decreased,and the permeability of blood-brain barrier decreased.MDA content in rat brain decreased and SOD activity increased.Western blot results showed that HIF-1α,VEGF,MMP-9,AQP4,SERT protein were significantly down-regulated.Conclusions Fluoxetine has protective effect on rats with brain edema at high altitude,and its mechanism may be related to improving oxidative stress,activating HIF-1α/VEGF/MMP-9 signaling pathway and affecting the expression of SERT protein.SERT may be a potential target for treating brain edema at high altitude.