Parecoxib Protects Mouse Cortical Neurons Against OGD/R Induced Neurotoxicity by Up-Regulating Bcl-2
Parecoxib Protects Mouse Cortical Neurons Against OGD/R Induced Neurotoxicity by Up-Regulating Bcl-2
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帕瑞昔布通过上调 Bcl-2 保护小鼠皮质神经元免受 OGD/R 诱导的神经毒性
DOI：
10.1007/s11064-015-1580-7
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发表时间：
2015-06
影响因子：
4.4
通讯作者：
Guo, Qulian
中科院分区：
文献类型：
--
作者：
Wang, Yueling;Ma, Wenjuan;Jia, Aijun;Guo, Qulian
缺血性中风仍然是一个重要的问题，是世界范围内死亡和残疾的主要原因。帕瑞昔布在临床上用于术后疼痛的短期管理。已报道在大鼠中施用帕瑞昔布可保护免受脑缺血/再灌注。然而，帕瑞昔布的神经保护机制在很大程度上仍然未知。在这项研究中，我们发现帕瑞昔布可以保护由4 h氧-葡萄糖剥夺（OGD）加再氧20 h诱导的神经毒性，这是一种广泛使用的体外缺血/再灌注模型。此外，我们还对帕瑞昔布神经保护作用的分子机制进行了研究。我们发现帕瑞昔布能够激活CREB，并随后维持Bcl-2的表达，这是一种重要的乳腺癌相关蛋白。通过转染Bcl-2-shRNA抑制内源性Bcl-2表达显著减弱了帕瑞昔布治疗的神经保护作用。ATP生成实验和线粒体膜电位（Δ Vm）实验表明，帕瑞昔布可能通过维持线粒体功能发挥抗OGD/R的作用。这些数据表明，帕瑞昔布治疗是一种潜在的治疗方法，防止缺血/再灌注损伤。
Ischemic stroke remains a significant problem that is the major cause of death and disability worldwide. Parecoxib is clinically used for short-term management of postoperative pain. Administration of parecoxib in rats has been reported to protect against the cerebral ischemia/reperfusion. However, the neuroprotective mechanism of parecoxib is still largely unknown. In this study, we found parecoxib could protect against neurotoxicity induced by 4 h oxygen–glucose deprivation (OGD) plus reoxgenation for 20 h, a widely used in vitro model of ischemia/reperfusion. In addition, we characterized the molecular mechanism of parecoxib’s neuroprotection. We found parecoxib was able to activate CREB, and subsequently maintained the expression of Bcl-2, which is an important mitochondria-associated protein. Inhibition of endogenous Bcl-2 expression by transfection of Bcl-2-shRNA significantly attenuated the neuroprotective effects of parecoxib treatment. Furthermore, ATP production assay and mitochondrial membrane potential (ΔΨm) assay suggested that parecoxib exerted neuroprotective effect against OGD/R by maintaining the function of mitochondria. These data suggested that parecoxib treatment is a potential therapeutic approach for protecting against ischemia/reperfusion injury.
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影响因子：
6.1
作者：
Na Wang;Q. Guo;Z. Ye;Ping-ping Xia;E. Wang;Ya-jing Yuan
通讯作者：
Na Wang;Q. Guo;Z. Ye;Ping-ping Xia;E. Wang;Ya-jing Yuan
DOI：
--
发表时间：
2007
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
K. Fuenzalida;R. Quintanilla;P. Ramos;Daniela Piderit;Rodrigo A Fuentealba;G. Martínez;N. Inestrosa;M. Bronfman
通讯作者：
K. Fuenzalida;R. Quintanilla;P. Ramos;Daniela Piderit;Rodrigo A Fuentealba;G. Martínez;N. Inestrosa;M. Bronfman
影响因子：
6.3
作者：
M. Nagayama;K. Niwa;T. Nagayama;M. E. Ross;C. Iadecola
通讯作者：
M. Nagayama;K. Niwa;T. Nagayama;M. E. Ross;C. Iadecola
DOI：
10.1097/00004647-200204000-00007
发表时间：
2002-04-01
影响因子：
6.3
作者：
Liu, D;Lu, CB;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
9.3
作者：
Kelsen J;Kjaer K;Chen G;Pedersen M;Røhl L;Frøkiaer J;Nielsen S;Nyengaard JR;Rønn LC
通讯作者：
Rønn LC