Salidroside alleviates high-glucose-induced injury in retinal pigment epithelial cell line ARPE-19 by down-regulation of miR-138

Diabetic retinopathy (DR) is a complication of diabetes leading cause of blindness in adults. Salidroside (SAL) is a main ingredient from <i>Rhodiola rosea L</i>., has been reported to have a beneficial protection on vascular function. However, whether SAL is a suitable treatment for DR remains unreported. The study aimed to investigate the effect of SAL on high-glucose (HG)-induced injury in ARPE-19 cells. ARPE-19 cells were managed with diverse concentrations of glucose, and constructed a model of HG-induced ARPE-19 cells injury. Then, SAL was employed to stimulate ARPE-19 cells, and cell viability, apoptosis, apoptosis-associated factors, the pro-inflammatory cytokines, and ROS levels were determined. The correlation between miR-138 and SIRT1 was predicated by bioinformatics software of TargetScan (http://www.targetscan.org/) and Dual luciferase reporter assay. MiR-138 mimic, inhibitor and NCs were transfected into ARPE-19 cells, and the impacts of miR-138 on HG-induced cell injury were investigated. PI3K/AKT and AMPK signalling pathways were examined to explore the underlying mechanism. The results disclosed that HG inhibited cell viability, promoted apoptosis, up-regulated IL-6 and TNF-α, as well as increased ROS level in ARPE-19 cells. But, SAL obviously alleviated HG-induced ARPE-19 cells injury. Repressed miR-138 was triggered by SAL, and SIRT1 was predicated as a direct target of miR-138. Overexpressed miR-138 declined the protective effect of SAL on HG-injured ARPE-19 cells. Besides, SAL activated PI3K/AKT and AMPK pathways by adjusting miR-138. In conclusions, SAL flattened HG-induced injury in ARPE-19 cells by repression of miR-138 and activating PI3K/AKT and AMPK pathways.

糖尿病视网膜病变（Diabetic retinopathy, DR）是糖尿病的并发症，也是成年人失明的主要诱因。红景天苷（Salidroside, SAL）是红景天（Rhodiola rosea L）的主要活性成分，据报道可对血管功能发挥有益的保护作用。然而，红景天苷是否可作为糖尿病视网膜病变的适宜治疗手段，目前仍未见相关报道。本研究旨在探究红景天苷对高糖（high-glucose, HG）诱导的ARPE-19细胞损伤的影响。实验中，我们采用不同浓度的葡萄糖处理ARPE-19细胞，构建了高糖诱导的ARPE-19细胞损伤模型。随后，使用红景天苷干预ARPE-19细胞，并检测细胞活力、细胞凋亡、凋亡相关因子、促炎细胞因子以及活性氧（ROS）水平。通过TargetScan生物信息学软件（http://www.targetscan.org/）及双荧光素酶报告基因实验，预测miR-138与SIRT1之间的靶向调控关系。将miR-138模拟物、抑制剂及阴性对照（NCs）转染至ARPE-19细胞，探究miR-138对高糖诱导的细胞损伤的影响。同时检测PI3K/AKT与AMPK信号通路的活化情况，以探索潜在的作用机制。实验结果显示，高糖处理可抑制ARPE-19细胞活力、促进细胞凋亡、上调白细胞介素-6（IL-6）与肿瘤坏死因子-α（TNF-α）的表达，并升高细胞内ROS水平。而红景天苷可显著缓解高糖诱导的ARPE-19细胞损伤。红景天苷可下调miR-138的表达，且生物信息学预测证实SIRT1是miR-138的直接靶基因。过表达miR-138会削弱红景天苷对高糖损伤ARPE-19细胞的保护作用。此外，红景天苷可通过调控miR-138的表达激活PI3K/AKT与AMPK信号通路。综上，红景天苷可通过下调miR-138的表达并激活PI3K/AKT与AMPK信号通路，减轻高糖诱导的ARPE-19细胞损伤。