Stachydrine Relieved the Inflammation and Promoted the Autophagy in Diabetes Retinopathy Through Activating the AMPK/SIRT1 Signaling Pathway
Jiewei Yu, Lingling Ke, Jingjing Zhou, Chunyan Ding, Hui Yang, Dongbiao Yan, Chengbi Yu
Abstract
Background: Diabetes retinopathy (DR) is a chronic, progressive, and potentially harmful retinal disease associated with persistent hyperglycemia. Autophagy is a lysosome-dependent degradation pathway that widely exists in eukaryotic cells, which has recently been demonstrated to participate in the DR development. Stachydrine (STA) is a water-soluble alkaloid extracted from Leonurus heterophyllus . This study aimed to explore the effects of STA on the autophagy in DR progression in vivo and in vitro. Methods: High glucose-treated human retinal microvascular endothelial cells (HRMECs) and STA-treated rats were used to establish DR model. The reactive oxygen species (ROS) and inflammatory factor levels (TNF-α, IL-1β, and IL-6) were determined using corresponding kits. Additionally, the cell growth was analyzed using CCK-8 and EdU assays. Besides, LC3BII, p62, p-AMPKα, AMPKα, and SIRT1 protein levels were measured using Western blot. The LC3BII and SIRT1 expressions were also determined using immunofluorescence. Results: The results showed that STZ decreased the ROS and inflammatory factor levels in the HG-treated HRMECs. Besides, after STA treatment, the beclin-1, LC3BII, p-AMPKα, and SIRT1 levels were increased, and p62 was decreased in the HG-treated HRMECs and the retinal tissue of STZ-treated rats. Conclusion: In conclusion, this study demonstrated that STA effectively relieved the inflammation and promoted the autophagy in DR progression in vivo and in vitro through activating the AMPK/SIRT1 signaling pathway. Keywords: diabetes retinopathy, stachydrine, autophagy, AMPK/SIRT1