PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage
PARP inhibition attenuates early brain injury through NF-κB/MMP-9 pathway in a rat model of subarachnoid hemorrhage
复制标题
PARP 抑制通过 NF-kappa B/MMP-9 通路减轻蛛网膜下腔出血大鼠模型的早期脑损伤
DOI：
10.1016/j.brainres.2016.05.005
复制
发表时间：
2016-08-01
期刊：
影响因子：
2.9
通讯作者：
Chen, Gao
中科院分区：
文献类型：
--
作者：
Chen, Ting;Wang, Wei;Chen, Gao
多聚腺苷二磷酸核糖聚合酶（Poly（ADP-ribose）polymerases，PARP）在多种神经系统疾病中发挥重要作用，但其在蛛网膜下腔出血（subarachnoid hemorrhage，SAH）后早期脑损伤中的作用尚不清楚。本研究旨在探讨PARP在SAH后早期脑损伤中的作用及其可能机制。将89只雄性SD大鼠随机分为假手术组、SAH+Vehicle组和SAH+PARP抑制剂（PJ 34）组。使用血管内穿孔模型诱导大鼠SAH。在SAH诱导后5分钟和8小时腹膜内施用PJ 34（10 mg/kg）或媒介物（0.9%NaCl）。观察死亡率、SAH分级、神经功能、伊文思蓝外渗、脑水肿、免疫荧光染色和蛋白印迹。PJ 34降低BBB通透性和脑水肿，改善神经功能，减轻SAH大鼠模型中的神经元细胞死亡。此外，PJ 34抑制NF-κ B的核转位，降低促炎细胞因子IL-1 β、IL-6和TNF-α的表达，降低MMP-9的表达，防止紧密连接蛋白的降解，并降低小胶质细胞活化。这些数据表明，PJ 34抑制PARP可能是SAH的重要治疗药物。(C)2016爱思唯尔B. V.保留所有权利。
Poly (ADP-ribose) polymerases (PARPs) play an important role in a range of neurological disorders, however, the role of PARP in early brain injury after subarachnoid hemorrhage (SAH) remains unclear. This study was designed to explore the role and the potential mechanisms of PARP in early brain injury after SAH. Eighty-nine male SD rats were randomly divided into the Sham group, SAH+Vehicle group and SAH+PARP inhibitor (PJ34) group. An endovascular perforation model was used to induce SAH in rats. PJ34 (10 mg/kg) or vehicle (0.9% NaCl) was intraperitoneally administered at 5 min and 8 h after SAH induction. Mortality, SAH grades, neurological function, evans blue extravasation, brain edema, immunofluorescence staining and western blotting were performed. PJ34 reduced BBB permeability and brain edema, improved neurological function and attenuated neuronal cell death in the rat model of SAH. Moreover, PJ34 inhibited the nuclear translocation of NF-kappa B, decreased the expression of the proinflammatory cytokines IL-1 beta, IL-6 and TNF-alpha, reduced the expression of MMP-9, prevented the degradation of tight junction proteins, and decreased microglia activation. These data indicated that PARP inhibition through PJ34 might be an important therapeutic drug for SAH. (C) 2016 Elsevier B.V. All rights reserved.