蒙药古日古木-13通过miR-187调控RGC氧化应激的机制研究

Glaucoma belongs to blinding neurodegenerative diseases and often is caused by pathological high intraocular pressure. Retinal ganglion cells (RGCs) damage is an important factor for glaucoma neurodegeneration. But the mechanism of optic nerve injury is still unclear. GuRiGuMu-13, one of Mongolian medicines, has been used for prevention of glaucoma optic nerve injury for many years in clinical research. In our previous work, miR-187 regulates RGC apoptosis through TGF-β signaling pathway. Our present study will focus on GuRiGuMu-13 and are going to detect proliferation and apoptosis of RGC under conditions of high pressure, Glu, H2O2 oxidative stress in presence of GuRiGuMu-13 by means of gene overexpression or gene interference, flow cytometry, Biological information analysis, luciferase report and RNA Array and other technical methods. We aim to explore the involvement of miR-187-mediated signaling pathways in anti-oxidative stress of GuRiGuMu-13. This study can eventually provide the experimental basis for elucidating the molecular pathological mechanism of GuRiGuMu-13 in the prevention and treatment of optic nerve injury, and also provide theory support for further promotion of Mongolian treatment in glaucoma.

青光眼(Glaucoma)是一种由病理性高眼压引发的致盲性神经退行性疾病。视网膜神经节细胞（Retinal ganglion cells，RGCs)损伤是青光眼神经退行性病变的一个重要因素。但视神经损伤机至今尚不明确。蒙药古日古木-13对于青光眼视神经损伤的防治作用具有多年的临床研究基础。课题组在前期研究中发现miR-187通过TGF-β信号通路调控RGC细胞凋亡。本课题在前期工作的基础上，拟在青光眼动物模型和RGCs细胞水平上，以古日古木-13为研究载体，利用基因过表达或干扰、流式细胞仪、生物信息分析、荧光素酶报告和RNA Array等技术方法，检测高压、Glu、H2O2氧化应激条件RGC增殖和凋亡的表达，探讨miR-187可调控的信号通路介导古日古木-13抗RGC氧化应激作用。最终为阐明古日古木-13防治视神经损伤的分子病理机制提供实验依据，为进一步推广蒙药治疗青光眼提供理论支持。

青光眼(Glaucoma)是一种由病理性高眼压引发的致盲性神经退行性疾病。视网膜神经节细胞（Retinal ganglion cells，RGCs)损伤是青光眼神经退行性病变的一个重要因素。但视神经损伤机至今尚不明确。蒙药古日古木-13对于青光眼视神经损伤的防治作用具有多年的临床研究基础。课题组建立青光眼动物模型和RGCs细胞，以古日古木-13为研究载体，利用基因过表达或干扰、流式细胞仪、生物信息分析、荧光素酶报告和RNA Array等技术方法，检测高压、Glu、H2O2氧化应激条件RGC增殖和凋亡的表达，探讨miR-187通过SMAD7调控青光眼诱导 RGC凋亡，通过P2RX7促进氧化应激诱导的视网膜细胞凋亡。并且进一步验证蒙药古日古木-13对青光眼小鼠视网膜神经节细胞凋亡的保护作用以及蒙药古日古木-13通过抑制P2RX7/p38MAPK信号通路，抑制氧化应激诱导视网膜神经节细胞凋亡等结果。最终为阐明古日古木13防治视神经损伤的分子病理机制提供实验依据，为进一步推广蒙药治疗青光眼提供理论支持。