期刊
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
卷 44, 期 5, 页码 586-594出版社
WILEY
DOI: 10.1111/1440-1681.12730
关键词
NAD(+); neuronal injury; PARP-1; ropivacaine
资金
- Fujian province hospital youth fund [2014YNQN09]
- Natural Science Foundation of Fujian Province [2016J01506]
Ropivacaine is one of the most common but toxic local anaesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and nicotinamide adenine dinucleotide (NAD)(+) depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD(+) level, and western blots were used to analyze the expression levels of PARP-1 and apoptosis-inducing factor (AIF) after ropivacaine treatments with different concentrations and durations. A PARP-1 inhibitor (PJ-34) was used to confirm the relationship between PARP-1 activation and NAD(+) depletion. Hoechst 33258 nuclear staining and a mitochondrial membrane potential (m) assay were used to detect the role of exogenous NAD(+) in ropivacaine-induced neuronal injury. Ropivacaine-induced SH-SY5Y cell death and apoptosis, PARP-1 activation, and AIF increase as well as intracellular NAD(+) depletion occurred in a time- and concentration-dependent manner (P<.05). PARP-1 activation led to NAD(+) depletion (P<.05). Exogenous NAD(+) impaired ropivacaine-induced nuclear injury (P<.05). Ropivacaine treatment induced PARP-1 activation and NAD(+) depletion (P<.05). Parthanatos (PARP-1-dependent cell death) was definitely involved in ropivacaine-induced neuronal injury, and exogenous NAD(+) may be a novel therapeutic method for parthanatos-dependent neuronal injury.
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