Diabetic retinopathy (DR) is the leading cause of decreased vision and blindness globally. The aim of this study was to understand the role of physcion 8-O-β-glucopyranoside (PG) in high glucose (HG)-induced DR and to investigate whether lncRNA NORAD/miR-125/STAT3 signalling was the underlying mechanism involved in DR. To this end, the serum levels of NORAD, miR-125, and STAT3 were determined in patients with DR. The APRE-19 cells were subjected to HG treatment to construct the cell model of DR. HG-disposed APRE-19 cell injury was assessed by detecting cell viability, apoptosis, concentrations of pro-inflammatory cytokines including TNF-α and IL-1β, and ROS generation. Moreover, the effect of PG on HG-disposed APRE-19 cell injury was investigated. NORAD was then overexpressed to investigate the combined effects of NORAD overexpression and PG on HG-disposed APRE-19 cell injury. Furthermore, the regulatory relationship between NORAD and miR-125 as well as miR-125 and STAT3 was investigated. The expression levels of NORAD and STAT3 were significantly increased in the serum of DR patients, while the miR-125 expression was decreased. The HG treatment-induced injury to APRE-19 cells, which were alleviated by PG treatment. Moreover, PG alleviated HG-disposed injury to ARPE-19 cells by decreasing NORAD. NORAD negatively regulated miR-125 expression and the combined effects of NORAD and PG on HG-disposed ARPE-19 cell injury were reversed by miR-125 overexpression. Furthermore, STAT3 was confirmed as a target gene of miR-125. Our results show that PG exerts protective roles in HG-disposed DR via regulating lncRNA NORAD/miR-125/STAT3 signalling. NORAD/miR-125/STAT3 axis may provide a novel perspective for target therapy of DR.

中文翻译：

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Physcion8-O-β-吡喃葡萄糖苷可通过调节lncRNA NORAD / miR-125 / STAT3信号传导在高糖诱导的糖尿病性视网膜病变中发挥保护作用。

糖尿病性视网膜病（DR）是全球视力和失明程度下降的主要原因。这项研究的目的是了解physcion8-O-β-吡喃葡萄糖苷（PG）在高糖（HG）诱导的DR中的作用，并研究lncRNA NORAD / miR-125 / STAT3信号是否是参与其中的潜在机制博士 为此，在DR患者中测定了NORAD，miR-125和STAT3的血清水平。对APRE-19细胞进行HG处理以构建DR的细胞模型。通过检测细胞活力，细胞凋亡，促炎性细胞因子（包括TNF-α和IL-1β）的浓度以及ROS的产生来评估HG处理的APRE-19细胞损伤。此外，研究了PG对HG处理的APRE-19细胞损伤的作用。然后过表达NORAD，以研究NORAD过表达和PG对HG引起的APRE-19细胞损伤的联合作用。此外，研究了NORAD与miR-125以及miR-125和STAT3之间的调节关系。DR患者血清中NORAD和STAT3的表达水平显着升高，而miR-125的表达则降低。HG处理诱导的APRE-19细胞损伤，通过PG处理得以缓解。此外，PG通过减少NORAD减轻了HG对ARPE-19细胞的损伤。miR-125的过表达逆转了NORAD对miR-125表达的负调控以及NORAD和PG对HG引起的ARPE-19细胞损伤的联合作用。此外，证实STAT3是miR-125的靶基因。我们的研究结果表明，PG通过调节lncRNA NORAD / miR-125 / STAT3信号传导在HG处理的DR中发挥保护作用。NORAD / miR-125 / STAT3轴可能为DR的靶向治疗提供新的视角。