Quercetin relieved diabetic neuropathic pain by inhibiting upregulated P2X4 receptor in dorsal root ganglia
Quercetin relieved diabetic neuropathic pain by inhibiting upregulated P2X4 receptor in dorsal root ganglia
复制标题
槲皮素通过抑制背根神经节中上调的 P2X(4) 受体缓解糖尿病神经性疼痛
DOI：
10.1002/jcp.27091
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Liang, Shangdong
中科院分区：
文献类型：
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作者：
Yang, Runan;Li, Lin;Liang, Shangdong
背根神经节 (DRG) 中表达的伤害性离子通道的上调有助于糖尿病疼痛症状的发展和保留。黄酮类槲皮素（3,3',4',5,7-五羟基黄酮）是从多种水果和蔬菜中提取的成分，具有抗炎、镇痛、抗癌、抗溃疡、降压等作用。然而，槲皮素镇痛作用的确切机制仍然知之甚少。本研究的目的是探讨槲皮素对2型糖尿病大鼠模型DRG中与P2X(4)受体相关的糖尿病神经病理性疼痛的影响。我们的数据显示，与未经治疗的糖尿病大鼠相比，接受槲皮素治疗的糖尿病大鼠的机械戒断阈值和热戒断潜伏期均较高。与对照大鼠相比，糖尿病大鼠DRG中P2X(4)信使RNA和蛋白的表达水平升高，而槲皮素治疗显着抑制了糖尿病大鼠这种增强的P2X(4)表达。卫星胶质细胞 (SGC) 包裹 DRG 中的神经元胞体。槲皮素治疗还降低了糖尿病大鼠 DRG 中 P2X(4) 和胶质纤维酸性蛋白（SGC 的标志物）的共表达升高，并降低了磷酸化 p38 丝裂原激活蛋白激酶 (p38MAPK) 的上调。槲皮素显着降低转染 P2X(4) 受体的 HEK293 细胞中 P2X(4) 激动剂三磷酸腺苷激活的电流。因此，我们的数据表明，槲皮素可能会降低 DRG SGC 中 P2X(4) 受体的上调，从而抑制 P2X(4) 受体介导的 p38MAPK 激活，从而缓解糖尿病大鼠的机械和热痛觉过敏。
The upregulation of nociceptive ion channels expressed in dorsal root ganglia (DRG) contributes to the development and retaining of diabetic pain symptoms. The flavonoid quercetin (3,3 ',4 ',5,7-pentahydroxyflavone) is a component extracted from various fruits and vegetables and exerts anti-inflammatory, analgesic, anticarcinogenic, antiulcer, and antihypertensive effects. However, the exact mechanism underlying quercetin's analgesic action remains poorly understood. The aim of this study was to investigate the effects of quercetin on diabetic neuropathic pain related to the P2X(4) receptor in the DRG of type 2 diabetic rat model. Our data showed that both mechanical withdrawal threshold and thermal withdrawal latency in diabetic rats treated with quercetin were higher compared with those in untreated diabetic rats. The expression levels of P2X(4) messenger RNA and protein in the DRG of diabetic rats were increased compared with the control rats, while quercetin treatment significantly inhibited such enhanced P2X(4) expression in diabetic rats. The satellite glial cells (SGCs) enwrap the neuronal soma in the DRG. Quercetin treatment also lowered the elevated coexpression of P2X(4) and glial fibrillary acidic protein (a marker of SGCs) and decreased the upregulation of phosphorylated p38 mitogen-activated protein kinase (p38MAPK) in the DRG of diabetic rats. Quercetin significantly reduced the P2X(4) agonist adenosine triphosphate-activated currents in HEK293 cells transfected with P2X(4) receptors. Thus, our data demonstrate that quercetin may decrease the upregulation of the P2X(4) receptor in DRG SGCs, and consequently inhibit P2X(4) receptor-mediated p38MAPK activation to relieve the mechanical and thermal hyperalgesia in diabetic rats.