人参皂苷 Rg1 通过 miR-489-3p/Sirt1 轴促进糖尿病足溃疡的愈合。
Ginsenoside Rg1 promoted the wound healing in diabetic foot ulcers via miR-489-3p/Sirt1 axis.
机构信息
Second Clinical Medical College, Southern Medical University, Guangzhou, 510515, Guangdong Province, PR China; Department of Rehabilitation, Guangdong Provincial People's Hospital, Guangzhou, 510515, Guangdong Province, PR China.
Department of Rehabilitation Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410016, Hunan Province, PR China; Department of Sports Medicine, Institute of Translational Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410016, Hunan Province, PR China.
出版信息
J Pharmacol Sci. 2021 Nov;147(3):271-283. doi: 10.1016/j.jphs.2021.07.008. Epub 2021 Aug 5.
PURPOSE
Diabetic foot ulcers (DFUs) are common complications of high severity for diabetes. Ginsenoside Rg1 (Rg1) has the potential for diabetes and cardiovascular diseases therapy. This research aimed at exploring the regulation of Rg1 on DFUs treatment and the underlying mechanism.
METHODS
Human umbilical vein endothelial cells (HUVECs) incubated with high-glucose culture medium were established for induction of diabetes model. The MTT assay, Annexin V/PI assay and oxidative stress detection were carried out on high-glucose-induced HUVECs. Dual-luciferase reporter assay was performed to prove the interaction of miR-489-3p and Sirt1. DFUs model was established to determine the efficiency of Rg1 and miR-489-3p in wound closure of DFUs in vivo.
RESULTS
Rg1 promoted cell proliferation, migration and angiogenesis, and reduced cell apoptosis in high-glucose-induced HUVECs. Knockdown of miR-489-3p alleviated the high-glucose-induced damage to HUVECs, while overexpression of miR-489-3p attenuated the protection effects of Rg1. Overexpression Sirt1 promoted wound healing in DFUs and Sirt1 was a direct target of miR-489-3p. In addition, animal experiments demonstrated that Rg1 promoted wound closure by regulating miR-489-3p/Sirt1 axis.
CONCLUSIONS
Rg1 alleviated the DFUs by increasing Sirt1 expression via miR-489-3p downregulation and promoting activation of PI3K/AKT/eNOS signaling.
目的
糖尿病足溃疡（DFUs）是糖尿病严重并发症之一。人参皂苷 Rg1（Rg1）具有治疗糖尿病和心血管疾病的潜力。本研究旨在探索 Rg1 对 DFUs 治疗的调节作用及其潜在机制。
方法
建立人脐静脉内皮细胞（HUVECs）在高糖培养培养基中孵育的糖尿病模型。对高糖诱导的 HUVECs 进行 MTT 检测、Annexin V/PI 检测和氧化应激检测。采用双荧光素酶报告基因检测证明 miR-489-3p 和 Sirt1 的相互作用。建立 DFUs 模型，以确定 Rg1 和 miR-489-3p 在体内 DFUs 伤口闭合中的效率。
结果
Rg1 促进了高糖诱导的 HUVECs 增殖、迁移和血管生成，并减少了细胞凋亡。miR-489-3p 的敲低减轻了高糖对 HUVECs 的损伤，而过表达 miR-489-3p 则减弱了 Rg1 的保护作用。Sirt1 的过表达促进了 DFUs 的伤口愈合，并且 Sirt1 是 miR-489-3p 的直接靶标。此外，动物实验表明，Rg1 通过调节 miR-489-3p/Sirt1 轴促进伤口闭合。
结论
Rg1 通过下调 miR-489-3p 增加 Sirt1 表达，促进 PI3K/AKT/eNOS 信号通路的激活，从而减轻 DFUs。
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