Salidroside ameliorates diabetic retinopathy and Müller cell inflammation via the PI3K/Akt/GSK-3β/NF-𝜅B pathway.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Vision Pub Date : 2024-02-10 eCollection Date: 2024-01-01

Zhen Feng, Yang Yang, Cai-Xing Shi, An-Qi Liu, Chuan-Ling Wu, Wen-Qiang Liu, Sheng-Xue Yu, Hong-Dan Yu, Zhong-Fu Zuo, Xue-Zheng Liu

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引用次数: 0

Abstract

Purpose: To determine whether salidroside (SAL) modulates inflammatory cytokines in rat retinal Müller cells (rMC-1) in a hyperglycemic environment by investigating the anti-inflammatory mechanisms of SAL in vitro and in vivo.

Methods: A streptozotocin (STZ)-induced diabetic rat model was established to examine the effects of SAL using hematoxylin and eosin (H&E) staining and immunohistochemistry. rMC-1 cells were grown in 50 mM of high-glucose medium. These simulated diabetic conditions were used to evaluate the anti-inflammatory effects of SAL using a Cell Counting Kit-8 (CCK-8) assay, immunofluorescence staining, western blotting, and real-time polymerase chain reaction (qRT‒PCR). H&E staining was used to analyze the number of ganglion cells in the retina. rMC-1 lysates were processed for qRT‒PCR to measure the steady-state mRNA expression levels of inflammatory markers, such as interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 1β (IL-1β). Western blot analysis and immunofluorescence staining were performed to determine the levels of these inflammatory markers.

Results: Our study showed that SAL reversed retinal ganglion cell loss and attenuated nuclear factor kappa B (NF-𝜅B) p65 translocation to the nucleus in STZ-induced diabetic rats. Incubating rMC-1 in different concentrations of SAL for 24 to 48 h affected cell viability. Furthermore, SAL treatment significantly decreased the protein levels of IL-6, TNF-α, and IL-1β compared with those in cells cultured in high glucose (HG). The mRNA expression levels of IL-6 and IL-1β were considerably reduced after SAL treatment, whereas the mRNA expression levels of IL-10 were significantly increased. Interestingly, the beneficial effects of SAL on HG-treated rMC-1 cells were abolished by the PI3K inhibitor LY294002.

Conclusions: These results indicate that SAL treatment reduces cytokine activation in cultured rMC-1. Furthermore, SAL prevents diabetic retinopathy (DR), in part, by modulating the PI3K/Akt/GSK-3β/NF-kB pathway to inhibit Müller cell activation. Thus, SAL is expected to be a potential agent for ameliorating the progression of DR.

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水杨甙通过PI3K/Akt/GSK-3β/NF-𝜅B途径改善糖尿病视网膜病变和Müller细胞炎症。

目的：通过研究柳氮磺吡啶（SAL）在体外和体内的抗炎机制，确定柳氮磺吡啶（SAL）是否能调节高血糖环境下大鼠视网膜Müller细胞（rMC-1）中的炎性细胞因子：方法：建立链脲佐菌素（STZ）诱导的糖尿病大鼠模型，使用苏木精和伊红（H&E）染色和免疫组织化学方法研究 SAL 的作用。在这些模拟糖尿病条件下，使用细胞计数试剂盒-8（CCK-8）检测法、免疫荧光染色法、Western 印迹法和实时聚合酶链反应（qRT-PCR）来评估 SAL 的抗炎作用。对 rMC-1 裂解液进行 qRT-PCR 处理，以测量白细胞介素 6（IL-6）、白细胞介素 10（IL-10）和白细胞介素 1β（IL-1β）等炎症标志物的稳态 mRNA 表达水平。结果表明，SAL能逆转视网膜的炎症反应：结果：我们的研究表明，SAL 逆转了 STZ 诱导的糖尿病大鼠视网膜神经节细胞的丧失，并减轻了核因子卡巴 B（NF-𝜅B）p65 向细胞核的转位。将 rMC-1 与不同浓度的 SAL 培养 24 至 48 小时会影响细胞活力。此外，与在高糖（HG）条件下培养的细胞相比，SAL 处理明显降低了 IL-6、TNF-α 和 IL-1β 的蛋白水平。经 SAL 处理后，IL-6 和 IL-1β 的 mRNA 表达水平明显降低，而 IL-10 的 mRNA 表达水平则明显升高。有趣的是，PI3K 抑制剂 LY294002 可取消 SAL 对 HG 处理的 rMC-1 细胞的有益作用：这些结果表明，SAL 处理可减少细胞因子在培养的 rMC-1 细胞中的激活。此外，SAL 部分通过调节 PI3K/Akt/GSK-3β/NF-kB 通路来抑制 Müller 细胞的活化，从而预防糖尿病视网膜病变（DR）。因此，SAL有望成为改善糖尿病视网膜病变进展的潜在药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.