Neuroprotective effect of 5α-androst-3β,5,6β-triol on retinal ganglion cells in a rat chronic ocular hypertension model
Neuroprotective effect of 5α-androst-3β,5,6β-triol on retinal ganglion cells in a rat chronic ocular hypertension model
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5α-androst-3β,5,6β-三醇对慢性高眼压模型大鼠视网膜神经节细胞的神经保护作用
DOI：
10.1016/j.neulet.2017.09.022
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发表时间：
2017-11-01
影响因子：
2.5
通讯作者：
Wang, Zhongfeng
中科院分区：
文献类型：
--
作者：
Chen, Yan-Qiu;Zhong, Shu-Min;Wang, Zhongfeng
以往的研究表明，5 α-雄甾-3 β，5，6 β-三醇（Triol），一种合成的类固醇化合物，在培养的皮层神经元中显示出显著的神经保护作用。在本研究中，我们探讨了三醇是否和如何对慢性高眼压（COH）大鼠模型的视网膜神经节细胞（RGCs）的神经保护作用。通过将超顺磁性氧化铁微珠注射到前房中来产生COH模型，并且给予Triol（4.8 μ g/100 g，i. p.，每日一次，持续4周）。免疫组化实验表明，在整个平卧COH视网膜，CTB标记的存活RGCs的数量进行性减少，而TUNEL阳性信号显着增加，从1至4周后的微珠注射。三醇给药显著减弱了CTB标记的RGCs数量的减少，并部分减少了COH视网膜中TUNEL阳性信号数量的增加。此外，三醇管理部分降低丙二醛（MDA）和活性氧（ROS）的水平，并显着拯救线粒体呼吸链复合物（MRCC）的活动在COH视网膜。我们的研究结果表明，三醇通过减少脂质过氧化和增强MRCCs的活性来防止COH视网膜RGCs的凋亡。
Previous studies have demonstrated that 5 alpha-androst-3 beta,5,6 beta-triol (Triol), a synthesized steroid compound, showed notable neuroprotective effect in cultured cortical neurons. In the present study, we explored whether and how Triol have neuroprotective effect on retinal ganglion cells (RGCs) in a chronic ocular hypertension (COH) rat model. COH model was produced by injecting superparamagnetic iron oxide micro-beads into the anterior chamber, and Triol was administrated (4.8 mu g/100 g, i.p., once daily for 4 weeks). Immunohistochemistry experiments showed that in whole flat-mounted COH retinas, the number of CTB-labeled survival RGCs was progressively reduced, while TUNEL-positive signals were significantly increased from 1 to 4 weeks after the micro-bead injection. Triol administration significantly attenuated the reduction in the number of CTB-labeled RGCs, and partially reduced the increased number of TUNEL-positive signals in COH retinas. Furthermore, Triol administration partially reduced the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and significantly rescued the activities of mitochondrial respiratory chain complex (MRCC) I/II/III in COH retinas. Our results suggest that Triol prevents RGCs from apoptotic death in COH retinas by reducing the lipid peroxidation and enhancing the activities of MRCCs.