The Neuroprotective Effects And Mechanisms Of Salvinorin A On The Ischemia Injury Of Rats

Objective: To observe the neuroprotective effects and mechanisms of Salvinorin A on the ischemia injury of rats.Methods:In vitro,primary rat cortex neurons were cultured and then oxygen-glucose deprivation(OGD)was performed.Then the neuroprotective effects of different doses of Salvinorin A were tested by measuring the lactate dehydrogenase(LDH)release.The optimal dose was selected for following studys.In order to investigate the mechanisms of Salvinorin A,three inhibitors of MAPK pathways,ERK pathway inhibitor U0126,P38 pathway inhibitor SB200235 and JNK pathway inhibitor SP600125,were added and the neuroprotective effects were tested again.In vivo,seven-day-old neonates were subjected to H/I.Neurological impairment was assessed progressively for 5 weeks after H/I by grid walking.Results: The LDH release of primary rat cortical neurons after oxygen-glucose deprivation was obviously increased compared with the control group.Salvinorin A showed obvious protective effects to the injury.And 1 ?M Salvinorin A was selected as the optimal dose because it is the lowest dose with obvious protective effect.Moreover,only the ERK pathway inhibitor U0126 can reverse the neuroprotective effect of Salvinorin A.In vivo,Salvinorin A improved neurological outcomes up to 5 weeks after neonatal H/I injury.Conclusion: Salvinorin A had dose dependently neuroprotective effects on the ischemia injury of rats.ERK/MAPK pathway was involved in the mechanism of the neuroprotective effects of Salvinorin A.