Neuroprotective Effect of Dauricine after Transient Middle Cerebral Artery Occlusion in Rats: Involvement of Bcl-2 Family Proteins

摘要

Previous studies have shown that the bisbenzyl isoquinoline alkaloid dauricinencan protect the brain against ischemic damage. We investigated here whether dauricine couldninhibit neuronal apoptosis and modulate Bcl-2 family protein levels in a rat model of transientnfocal cerebral ischemia. Male Sprague-Dawley rats underwent a 60min temporary occlusionnof the middle cerebral artery (MCAO). Two doses of dauricine (5 and 10 mg/kg as low andnhigh dose respectively) were administered intraperitoneally at 1 hour after MCAO. Afternneurological deficits were assessed at 3 hours and 24 hours of reperfusion, rats were killednand brain samples were collected. Apoptotic changes were evaluated by TUNEL method.nThe immunohistochemistry and Western blot were used to assess the protein expressions ofnBcl-2 and Bax. RT-PCR was used to determine Bcl-2 and Bax mRNA expressions. Dauricinen(5 and 10mg/kg) treatment improved neurological deficits, diminished DNA fragmentation,nincreased Bcl-2 expression and reduced Bax expression in the penumbra. The infarct-reducingneffects of dauricine may be due, in part, to the inhibition of apoptotic cell death via modulationnBcl-2 family protein in the penumbra