Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors.
Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors.
复制标题
辣椒素通过下调 NMDA 受体保护皮质神经元免受缺血/再灌注损伤
DOI：
10.1016/j.expneurol.2017.05.001
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发表时间：
2017-09
影响因子：
5.3
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Huang M;Cheng G;Tan H;Qin R;Zou Y;Wang Y;Zhang Y
辣椒素是辣椒产生辣味的成分，被广泛用于疼痛的研究和治疗。近期，多项研究阐述了它的神经保护作用。在此，我们研究了辣椒素神经保护作用的潜在机制。在大鼠大脑中动脉闭塞（MCAO）/再灌注模型中，将辣椒素（1或3纳摩尔）直接注射到梗死周围区域可减少梗死体积，并改善神经行为评分和运动协调功能。辣椒素的保护作用时间窗在再灌注后1小时内，此时兴奋性毒性是细胞死亡的主要原因。在培养的皮质神经元中，给予辣椒素可减轻谷氨酸诱导的兴奋性毒性损伤。关于辣椒素神经保护作用的机制，在皮质神经元中，辣椒素预处理后观察到谷氨酸刺激后的钙内流减少。瞬时受体电位香草酸亚型1（Trpv1）基因敲除消除了辣椒素对谷氨酸诱导的钙内流和随后神经元死亡的抑制作用。在皮质神经元中，辣椒素处理后检测到N - 甲基 - D - 天冬氨酸（NMDA）受体亚单位GluN1和GluN2B的表达降低。总之，我们的研究表明，辣椒素在皮质神经元中的神经保护作用依赖于TRPV1，并且NMDA受体表达和功能的下调有助于辣椒素提供的保护作用。
Capsaicin, the ingredient responsible for the pungent taste of hot chili peppers, is widely used in the study and management of pain. Recently, its neuroprotective effect has been described in multiple studies. Herein, we investigated the underlying mechanisms for the neuroprotective effect of capsaicin. Direct injection of capsaicin (1 or 3 nmol) into the peri-infarct area reduced the infarct volume and improved neurological behavioral scoring and motor coordination function in the middle cerebral artery occlusion (MCAO)/reperfusion model in rats. The time window of the protective effect of capsaicin was within 1 h after reperfusion, when excitotoxicity is the main reason of cell death. In cultured cortical neurons, administration of capsaicin attenuated glutamate-induced excitotoxic injury. With respect to the mechanisms of the neuroprotective effect of capsaicin, reduced calcium influx after glutamate stimulation was observed following capsaicin pretreatment in cortical neurons. Trpv1 knockout abolished the inhibitory effect of capsaicin on glutamate-induced calcium influx and subsequent neuronal death. Reduced expression of GluN1 and GluN2B, subunits of NMDA receptor, was examined after capsaicin treatment in cortical neurons. In summary, our studies reveal that the neuroprotective effect of capsaicin in cortical neurons is TRPV1-dependent and down-regulation of the expression and function of NMDA receptors contributes to the protection afforded by capsaicin.
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影响因子：
3.3
作者：
de Novellis V;Vita D;Gatta L;Luongo L;Bellini G;De Chiaro M;Marabese I;Siniscalco D;Boccella S;Piscitelli F;Di Marzo V;Palazzo E;Rossi F;Maione S
通讯作者：
Maione S
影响因子：
9.3
作者：
Abdelhamid, Ramy E.;Kovacs, Katalin J.;Nunez, Myra G.;Larson, Alice A.
通讯作者：
Larson, Alice A.
影响因子：
3.5
作者：
Lee, Kuang-Li;Lee, Chia-Wei;Wei, Pei-Kuen
通讯作者：
Wei, Pei-Kuen
影响因子：
4.3
作者：
Lee, Jong-Geol;Yon, Jung-Min;Nam, Sang-Yoon
通讯作者：
Nam, Sang-Yoon
DOI：
10.1152/ajpregu.00329.2013
发表时间：
2014-01-01
影响因子：
2.8
作者：
Cao, Zhijuan;Balasubramanian, Adithya;Marrelli, Sean P.
通讯作者：
Marrelli, Sean P.