Wang Bin, Tian Shilai, Wang Jiayi, Han Feng, Zhao Lei, Wang Rencong, Ning Weidong, Chen Wei, Qu Yan
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China; Department of Clinical Medicine, School of Aerospace Medicine, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Department of Neurosurgery, Xi Jing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi׳an 710032, China.
Brain Res. 2015 Jul 30;1615:89-97. doi: 10.1016/j.brainres.2015.04.033. Epub 2015 Apr 29.
Recent studies demonstrate that Thioredixin (Trx) possesses a neuronal protective effect and closely relates to oxidative stress and apoptosis of cerebral ischemia injury. The present study was conducted to validate the neuroprotective effect of recombinant human Trx-1 (rhTrx-1) and its potential mechanisms against ischemia injury at middle cerebral artery occlusion (MCAO) in mice. rhTrx-1 was administrated intraperitoneally at a dose of 5, 10 and 20mg/kg 30 min before MCAO in mice, and its neuronal protective effect was evaluated by neurological deficit score, brain dry-wet weight, 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein carbonyl content and HO-1 were detected to investigate its potential anti-oxidative and anti-inflammatory property, and the anti-apoptotic ability of rhTrx-1 was assessed by casepase-3 and TUNEL staining. The results demonstrated that rhTrx-1 significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death at 24h after MCAO. Moreover, rhTrx-1 resulted in a significant decrease in carbonyl contents and HO-1 against oxidative stress, which turned to be fast reduction during the first 24h and tended to be stable from 24h to 72h after MCAO. The study shows that rhTrx-1 exerts an neuroprotective effect in cerebral ischemia injury. The anti-oxidative, anti-apoptotic and anti-inflammatory properties of rhTrx-1 are more likely to succeed as a therapeutic approach to diminish oxidative stress-induced neuronal apoptotic cell death in acute ischemic stroke.
近期研究表明，硫氧还蛋白（Trx）具有神经保护作用，且与脑缺血损伤的氧化应激及细胞凋亡密切相关。本研究旨在验证重组人Trx-1（rhTrx-1）对小鼠大脑中动脉闭塞（MCAO）所致缺血损伤的神经保护作用及其潜在机制。在小鼠MCAO前30分钟，以5、10和20mg/kg的剂量腹腔注射rhTrx-1，通过神经功能缺损评分、脑干湿重、2,3,5-三苯基氯化四氮唑（TTC）染色评估其神经保护作用。检测蛋白质羰基含量和血红素加氧酶-1（HO-1）以研究其潜在的抗氧化和抗炎特性，通过半胱天冬酶-3（caspase-3）和TUNEL染色评估rhTrx-1的抗凋亡能力。结果表明，rhTrx-1在MCAO后24小时显著改善神经功能，减少脑梗死和凋亡细胞死亡。此外，rhTrx-1可显著降低羰基含量并对抗氧化应激的HO-1产生影响，在MCAO后的最初24小时内迅速降低，在24小时至72小时趋于稳定。该研究表明，rhTrx-1在脑缺血损伤中发挥神经保护作用。rhTrx-1的抗氧化、抗凋亡和抗炎特性更有可能成为减轻急性缺血性卒中氧化应激诱导的神经元凋亡细胞死亡的治疗方法。
