Wu Jiangchun, Wang Ruobing, Yang Dianxu, Tang Wenbin, Chen Zeli, Sun Qinglei, Liu Lin, Zang Rongyu
Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Department of Ophthalmology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.
Biochem Biophys Res Commun. 2018 Jan 22;495(4):2462-2468. doi: 10.1016/j.bbrc.2017.12.146. Epub 2017 Dec 27.
Retinal ischemia/reperfusion injury (IRI) plays a crucial role in the pathophysiology of various ocular diseases. Our previous study have shown that postconditioning with inhaled hydrogen (H) (HPC) can protect retinal ganglion cells (RGCs) in a rat model of retinal IRI. Our further study aims to investigate potential mechanisms underlying HPC-induced protection. Retinal IRI was performed on the right eyes of rats and was followed by inhalation of 67% H mixed with 33% oxygen immediately after ischemia for 1 h daily for one week. RGC density was counted using haematoxylin and eosin (HE) staining, retrograde labelling with cholera toxin beta (CTB) and TUNEL staining, respectively. Visual function was assessed using flash visual evoked potentials (FVEP) and pupillary light reflex (PLR). The phosphorylated Akt was analysed by RT-PCR and western blot. The results showed that administration of HPC significantly inhibited the apoptosis of RGCs and protected the visual function. Simultaneously, HPC treatment markedly increased the phosphorylations of Akt. Blockade of PI3K activity by inhibitors (LY294002) dramatically abolished its anti-apoptotic effect and lowered both visual function and Akt phosphorylation levels. Taken together, our results demonstrate that HPC appears to confer neuroprotection against retinal IRI via the PI3K/Akt pathway.
视网膜缺血/再灌注损伤（IRI）在多种眼部疾病的病理生理学中起关键作用。我们之前的研究表明，吸入氢气（H）进行后处理（HPC）可在视网膜IRI大鼠模型中保护视网膜神经节细胞（RGCs）。我们进一步的研究旨在探讨HPC诱导保护作用的潜在机制。对大鼠右眼进行视网膜IRI，缺血1小时后立即每天吸入67% H与33%氧气混合气体，持续一周。分别使用苏木精和伊红（HE）染色、霍乱毒素β（CTB）逆行标记和TUNEL染色计数RGC密度。使用闪光视觉诱发电位（FVEP）和瞳孔对光反射（PLR）评估视觉功能。通过RT-PCR和蛋白质印迹分析磷酸化的Akt。结果表明，给予HPC可显著抑制RGCs凋亡并保护视觉功能。同时，HPC处理显著增加了Akt的磷酸化。用抑制剂（LY294002）阻断PI3K活性可显著消除其抗凋亡作用，并降低视觉功能和Akt磷酸化水平。综上所述，我们的结果表明，HPC似乎通过PI3K/Akt途径对视网膜IRI具有神经保护作用。
