| Background and Objective: Recent studies have found that rifampicin decreases oxidative stress and exerts neuroprotective properties in neurodegenerative diseases. The Nrf2 has been considered a potential target for neuroprotection. In this study we examine whether rifampicin exhibits beneficial effect mediated by Nrf2 pathway after GCI.Methods: Rats were randomly assigned to four groups: sham group, 3 treatment groups with global ischemia [control(I/R group), rifampicin(Rif group), rifampicin plus brusatol(Rif+Bru group)]. Rats were subjected to transient GCI induced by bilateral common carotid artery occlusion for 20 min with systemic hypotension by blood withdrawal. Morris water maze test was performed for neurobehavioral test, the pathologic changes were showed by HE and TUNEL staining. The protein expression of Nrf2, HO-1 and COX-2 in hippocampus were analyzed by western blotting. The immunofluorescence staining was used to determine the distribution of Nrf2.Results: Rifampicin treatment significantly improved the spatial learning ability as compared to I/R group, which were consistent with the pathological changes. In addition, rifampicin significantly elevated the nuclear expression of Nrf2 and Nrf2 downstream anti-oxidant protein, HO-1, versus I/R group, meanwhile downregulated the expression of COX-2 in the hippocampus on day 3 after GCI. Interestingly, the forenamed effects of rifampicin were abolished by pretreatment with brusatol, an specific inhibitor of Nrf2 activation.Conclusions: These findings provide evidence that rifampicin exerts neuroprotective effects against global cerebral ischemia injury, which may be attributed to activation of the Nrf2 pathway. |
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