期刊
BRAIN SCIENCES
卷 9, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/brainsci9120378
关键词
middle cerebral artery occlusion (MCAO); chlorpromazine and promethazine (C+P); neuroprotection; reperfusion
资金
- National Nature Science Foundation of China [81871838, 81802231]
- Beijing Tongzhou District Financial Fund
- Science and Technology Plan of Beijing Tongzhou District [KJ2019CX005-05/13, KJ2018CX006]
- Youth Plan of Beijing Luhe Clinical Institute, Capital Medical University [LHYY2019-JC01]
Phenothiazine treatment has been shown to reduce post-stroke ischemic injury, though the underlying mechanism remains unclear. This study sought to confirm the neuroprotective effects of phenothiazines and to explore the role of the NOX (nicotinamide adenine dinucleotide phosphate oxidase)/Akt/PKC (protein kinase C) pathway in cerebral apoptosis. Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) for 2 h and were randomly divided into 3 different cohorts: (1) saline, (2) 8 mg/kg chlorpromazine and promethazine (C+P), and (3) 8 mg/kg C+P as well as apocynin (NOX inhibitor). Brain infarct volumes were examined, and cell death/NOX activity was determined by assays. Western blotting was used to assess protein expression of kinase C-delta (PKC-delta), phosphorylated Akt (p-Akt), Bax, Bcl-XL, and uncleaved/cleaved caspase-3. Both C+P and C+P/NOX inhibitor administration yielded a significant reduction in infarct volumes and cell death, while the C+P/NOX inhibitor did not confer further reduction. In both treatment groups, anti-apoptotic Bcl-XL protein expression generally increased, while pro-apoptotic Bax and caspase-3 proteins generally decreased. PKC protein expression was decreased in both treatment groups, demonstrating a further decrease by C+P/NOX inhibitor at 6 and 24 h of reperfusion. The present study confirms C+P-mediated neuroprotection and suggests that the NOX/Akt/PKC pathway is a potential target for efficacious therapy following ischemic stroke.
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