Histamine H3 receptor antagonist Clobenpropit protects propofol-induced apoptosis of hippocampal neurons through PI3K/AKT pathway

W. He, Q.-H. Yuan, Q. Zhou

Department of Anaesthesiology, Mianyang Central Hospital, Mianyang, China. 278523276@qq.com

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• Pharmacology

OBJECTIVE: The aim of the study was to explore whether histamine H3 receptor antagonist Clobenpropit could protect propofol-induced neurotoxicity in hippocampal neurons.

MATERIALS AND METHODS: Hippocampal neurons were extracted from neonatal rats and induced with propofol. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed to detect apoptotic rate of neurons. Western blot was conducted to detect protein levels of cleaved-caspase-3 and Bax/Bcl2. After LY294002 treatment, the PI3K pathway antagonist was applied in neurons, protein levels of cleaved-caspase-3 and Bax/Bcl2 were detected by Western blot as well.

RESULTS: Propofol treatment remarkably induced neuronal apoptosis. Clobenpropit alleviated cell apoptosis induced by propofol. Protein expressions of cleaved-caspase-3 and Bax/Bcl2 were remarkably downregulated in neurons treated with Clobenpropit. LY294002 induction remarkably reverses the protective role of Clobenpropit in neuronal apoptosis, manifesting as downregulated PI3K and p-AKT after LY294002 treatment.

CONCLUSIONS: Clobenpropit protects propofol-induced neuronal apoptosis through activating PI3K/AKT pathway.

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