Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell
Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell
复制标题
甲苯噻嗪对Wistar大鼠和PC12细胞镇静镇痛的分子机制
DOI：
10.1538/expanim.18-0167
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发表时间：
2019-04
影响因子：
2.4
通讯作者：
Li gao
中科院分区：
文献类型：
--
作者：
Jinghua Zhao;Yiming Zhang;Wenhan Liu;Yu Chen;Daiyue Chang;Xintong Zhang;Tian Chang;Qi Wang;Tao Liu;Li gao
在兽医诊所，甲苯噻嗪通常用作镇静剂、镇痛剂，产生肌肉松弛。在这项研究中，我们的目的是探讨赛拉嗪在体内和体外的作用机制。在确定赛拉嗪的最佳剂量后，将35只雄性Wistar大鼠分为7组（n=5/组），包括对照组（生理盐水）和赛拉嗪给药组。然后，在甲苯噻嗪给药后的6个时间点，评价指标的变化。将PC 12细胞与甲苯噻嗪共培养，转染细胞外调节蛋白激酶（ERK）siRNA和蛋白激酶A（PKA）siRNA，观察相关指标的变化。我们的数据表明，甲苯噻嗪影响三磷酸腺苷（ATP）酶和环磷酸腺苷（cAMP）的水平，并调节GluR 1，ERK，PKA，cAMP反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）在神经系统中的表达。然而，甲苯噻嗪没有显着影响GluR 2和蛋白激酶C（PKC）的表达。总之，这些结果表明，甲苯噻嗪可能通过调节PKA/ERK/CREB信号通路发挥镇静和镇痛作用。
In veterinary clinics, xylazine is commonly used as a sedative, analgesic agent that produces muscle relaxation. In this study, we aimed to explore the mechanism of action of xylazine both in vivo and in vitro. After determing the optimal dose of xylazine, 35 male Wistar rats were divided into seven groups (n=5 per group), including a control group (saline) and xylazine administration groups. Then, at six time points after xylazine administration indicators were evaluated for changes. Moreover, PC12 cells were co-cultured with xylazine, and extracellular regulated protein kinase (ERK) siRNA and protein kinase A (PKA) siRNA were transfected into cells to identify changes of relevant indicators. Our data showed that xylazine influenced the level of adenosine triphosphate (ATP) ase and cyclic adenosine monophosphate (cAMP), and regulated the expression of GluR1, ERK, PKA, cAMP-response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) in the nervous system. However, xylazine did not significantly affect the expression of GluR2 and protein kinase C (PKC). Together, these results indicated that xylazine might exert sedation and analgesia by regulating the PKA/ERK/CREB signaling pathway.
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影响因子：
2.9
作者：
Nair A;Vaidya VA
通讯作者：
Vaidya VA
DOI：
--
发表时间：
1977
期刊：
Farmakologiia i toksikologiia
影响因子：
--
作者：
Vagin IuE;Kovrizhnykh Va
通讯作者：
Vagin IuE;Kovrizhnykh Va
影响因子：
3.4
作者：
Bender, RA;Lauterborn, JC;Baram, TZ
通讯作者：
Baram, TZ
影响因子：
13.6
作者：
T. Yamashima
通讯作者：
T. Yamashima
影响因子：
3.5
作者：
Alhaider, Ibrahim A.;Aleisa, Abdulaziz M.;Alkadhi, Karim A.
通讯作者：
Alkadhi, Karim A.