Cyclosporin A ameliorates early brain injury after subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis pathway
Cyclosporin A ameliorates early brain injury after subarachnoid hemorrhage through inhibition of a Nur77 dependent apoptosis pathway
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DOI：
10.1016/j.brainres.2014.01.052
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发表时间：
2014-03-27
期刊：
影响因子：
2.9
通讯作者：
Shi, Jixin
中科院分区：
文献类型：
--
作者：
Dai, Yuxiang;Sun, Qing;Shi, Jixin
Nur 77是孤儿核受体超家族的一个有效的促凋亡成员。已经证明，它可以介导许多系统细胞对细胞外刺激的凋亡反应。我们先前的研究发现Nur 77介导的凋亡也参与了实验性蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）。Nur 77抑制剂CsA可阻断Nur 77的DNA结合活性，进而抑制Nur 77依赖的凋亡途径。CsA具有神经保护作用，在缺血性脑卒中和创伤性脑损伤中已被证实。因此，本研究旨在探讨CsA对SAH后EBI的神经保护作用。成年雄性SD大鼠随机分为4组：（1）对照组（n=24）;（2）SAN组（n = 24）;（3）SAH+DMSO组（n =24）;（4）SAH+CsA组（n=24）。CsA可明显降低Nur 77、p-Nur 77、Bcl-2和cyto C的表达，抑制细胞凋亡。预防性应用CsA后，神经功能缺损改善，脑水肿减轻，EBI改善。CsA可使脑皮质TUNEL阳性细胞明显减少。提示CsA对SAH后早期的神经保护作用可能与其抑制Nur 77依赖的凋亡途径有关。(C)2014爱思唯尔有限公司版权所有。
Nur77 is a potent pro-apoptotic member of the orphan nuclear receptor superfamily. It has been demonstrated that can mediate apoptosis in many system cells in response to extracellular stimuli. Our previous study revealed Nur77-mediated apoptotic also involved in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). CsA, a Nur77 inhibitor, can abolish DNA binding activity of Nur77, further inhibit the Nur77 dependent apoptosis pathway. CsA has the neuroprotective effects and has been demonstrated in ischemic stroke and traumatic brain injury. Hence, in this study was designed to explore the neuroprotective effects of CsA in EBI after SAH. Adult male SD rats were randomly assigned to four groups: (1) control group (n=24); (2) SAN (n=24); (3) SAH+DMSO group (n=24); and (4) SAH+CsA (n=24), 10 mg/kg of CsA or same volume of DMSO was administered by femoral vein injection at 15 min before SAN. CsA markedly decreased expressions of Nur77, p-Nur77, Bcl-2 and cyto C, and inhibited apoptosis. Improvement of neurological deficit, alleviation of brain edema and amelioration of EBI were obtained after prophylactic use of CsA. TUNEL-positive cells were reduced markedly in brain cortex by CsA. These findings suggest that neuroprotective effects of CsA during early peroid after SAH may be related to its inhibition of Nur77 dependent apoptosis pathway. (C) 2014 Elsevier B.V. All rights reserved.