Ha Park Joon, Yoo Ki-Yeon, Hye Kim In, Cho Jeong-Hwi, Lee Jae-Chul, Hyeon Ahn Ji, Jin Tae Hyun, Chun Yan Bing, Won Kim Dae, Kyu Park Ok, Kwon Seung-Hae, Her Song, Su Kim Jin, Hoon Choi Jung, Hyun Lee Choong, Koo Hwang In, Youl Cho Jae, Hwi Cho Jun, Kwon Young-Guen, Ryoo Sungwoo, Kim Young-Myeong, Won Moo-Ho, Jun Kang Il
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Department of Oral Anatomy, College of Dentistry and Research institute of Oral Biology, Gangneung-Wonju National University, Gangneung 25457, South Korea
Toxicol Sci. 2016 Dec;154(2):430-441. doi: 10.1093/toxsci/kfw167. Epub 2016 Aug 31.
Hydroquinone (HQ), a major benzene metabolite, occurs naturally in various plants and is manufactured for commercial use. Although HQ displays various biological effects, its neuroprotective effects following ischemic insults have not been investigated. In this study, we first examined neuroprotective effects of HQ in a rat model of transient focal cerebral ischemia. Animals were subjected to transient middle cerebral artery occlusion for 120 min. HQ (50 or 100 mg/kg) or vehicle was intraperitoneally administered once at 30 min after ischemia-reperfusion. Neuroprotection by treatment with 100 mg/kg of HQ was shown using evaluation of neurological deficits, positron-emission tomography (PET) and 2,3,5-triphenyltetrazoliumchloride (TTC) staining. In addition, HQ treatment significantly attenuated ischemia-induced Evans blue dye extravasation from blood vessels and significantly increased immunoreactivities of SMI-71 (an endothelial BBB marker) and glucose transporter-1 (GLUT-1, an endothelial cell marker) in ischemic cortex compared to the vehicle-treated ischemia-operated group. Confocal microscopy and western blot analysis also showed that HQ treatment maintained expressions of tight junction proteins (zonula occludens-1 and occludin) in the ischemic cortex. Post-treatment with HQ protected neurons from transient focal cerebral ischemic injury and the neuroprotective effect of HQ might be closely associated with prevention of BBB disruption via maintaining SMI-71 and GLUT-1 expressions as well as prevention of the degradation of zonula occludens-1 and occludin proteins.
对苯二酚（HQ）是苯的一种主要代谢产物，天然存在于多种植物中，并用于商业生产。尽管HQ具有多种生物学效应，但其在缺血性损伤后的神经保护作用尚未得到研究。在本研究中，我们首先在短暂性局灶性脑缺血大鼠模型中检测了HQ的神经保护作用。对动物进行120分钟的大脑中动脉短暂闭塞。在缺血再灌注后30分钟，腹腔注射一次HQ（50或100mg/kg）或溶剂。通过评估神经功能缺损、正电子发射断层扫描（PET）和2,3,5-三苯基氯化四氮唑（TTC）染色，显示100mg/kg的HQ治疗具有神经保护作用。此外，与溶剂处理的缺血手术组相比，HQ治疗显著减轻了缺血诱导的伊文思蓝染料从血管外渗，并显著增加了缺血皮层中SMI-71（一种内皮血脑屏障标志物）和葡萄糖转运蛋白-1（GLUT-1，一种内皮细胞标志物）的免疫反应性。共聚焦显微镜和蛋白质印迹分析还表明，HQ治疗维持了缺血皮层中紧密连接蛋白（闭合蛋白-1和闭合蛋白）的表达。HQ治疗后可保护神经元免受短暂性局灶性脑缺血损伤，HQ的神经保护作用可能与通过维持SMI-71和GLUT-1的表达预防血脑屏障破坏以及预防闭合蛋白-1和闭合蛋白的降解密切相关。
