右美托咪定
神经保护
药理学
纹状体
多巴胺
乙酰化
化学
兴奋剂
内科学
医学
受体
生物化学
镇静
基因
作者
Hu Sp,Jin Zhao,Wenxian Wang,Liu Y,Huifeng Wu,C Chen,Lei Yu,Gui Jb
标识
DOI:10.1177/0960327116652458
摘要
Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedation, anesthetic sparing, analgesia, sympatholytic, and neuroprotective properties. This study evaluated neuroprotective effects of dexmedetomidine on dopamine neurons correlated to histone acetylation via extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) pathway. Animals were randomly assigned to four groups and treatments were given as onetime doses: dimethyl sulfoxide (DMSO; n = 6), dexmedetomidine 1 mg/kg ( n = 6), 10 mg/kg ( n = 6), and 100 mg/kg ( n = 6). Acetylation histone protein levels and ERK protein levels in rats dopamine neuron from striatum were determined by Western blotting after various doses of dexmedetomidine (1, 10, and 100 mg/kg) treatments. The messenger RNA expression related to signal transduction coupled to 5-hydroxytryptamine receptor (5-HTR) in striatum was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Dexmedetomidine administration increased expression of ERK1/2 phosphorylation and histones H3 acetylation. PD098059, an inhibitor of pERK1/2, almost completely blocked dexmedetomidine-induced histones H3 acetylation. In addition, bioinformatics analysis in combination with qRT-PCR demonstrated that dexmedetomidine could regulate the genes that are related to signal transduction coupled to 5-HTR via α2-adrenoceptor. Our results define dexmedetomidine as a modulator of histones H3 acetylation via ERK1/2 signaling pathway in dopamine neuron from striatum, which may provide clues for the mechanism underlying the neuroprotective effects of dexmedetomidine.
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