丹酚酸 A 通过下调 CYLD 抑制 OX-LDL 加重脉络膜新生血管的作用。
Salvianolic Acid A Inhibits OX-LDL Effects on Exacerbating Choroidal Neovascularization via Downregulating CYLD.
机构信息
Department of Ophthalmology, Affiliated First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Oxid Med Cell Longev. 2017;2017:6210694. doi: 10.1155/2017/6210694. Epub 2017 Sep 1.
BACKGROUNDS
Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A.
METHODS
C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week. CNV was induced by laser; CNV severity was analyzed by fundus fluorescein angiography, H&E staining, and choroid flat mount after 1 week. In in vitro experiments, ARPE-19 and HUVECs were cultured with OX-LDL (with or without Sal A) for 48 hours. Angiogenic proteins, cell junction integrity, and tube formation were measured. siRNA and specific inhibitors were used to explore mechanisms of CYLD in promoting OX-LDL-induced CNV progression.
RESULTS
OX-LDL promoted laser-induced CNV volume by increasing VEGF, PDGF, and CYLD levels. Sal A antagonized OX-LDL effects and restrained CNV progression by decreasing VEGF/PDGF/CYLD, increasing antiangiostatin levels, and promoting P62-CYLD-TRAF6 interaction.
CONCLUSIONS
We demonstrated oxidation damage exacerbates CNV progression, and Sal A could be a clinical therapeutic reagent to exudative AMD.
背景
年龄相关性黄斑变性与脂质氧化密切相关，而 OX-LDL 与脉络膜新生血管的关系尚不清楚。最近，圆柱瘤病被证明能调节血管生成。然而，其在 CNV 进展中的作用尚不清楚。丹酚酸 A 广泛应用于血管疾病。我们研究了 OX-LDL 与 CNV 的关系，并探讨了 Sal A 的抗血管生成机制。
方法
将 C57BL6/J 小鼠随机分为四组，分别注射 PBS 或 OX-LDL，并与 Sal A 一起注射一周。激光诱导 CNV；1 周后通过眼底荧光血管造影、H&E 染色和脉络膜平铺分析 CNV 严重程度。在体外实验中，用 OX-LDL（有或没有 Sal A）培养 ARPE-19 和 HUVECs 48 小时。测量血管生成蛋白、细胞连接完整性和管形成。用 siRNA 和特异性抑制剂探讨 CYLD 在促进 OX-LDL 诱导的 CNV 进展中的作用机制。
结果
OX-LDL 通过增加 VEGF、PDGF 和 CYLD 水平促进激光诱导的 CNV 体积。Sal A 通过降低 VEGF/PDGF/CYLD、增加抗血管生成素水平、促进 P62-CYLD-TRAF6 相互作用来拮抗 OX-LDL 的作用，从而抑制 CNV 进展。
结论
我们证明氧化损伤加剧了 CNV 的进展，Sal A 可能是治疗渗出性 AMD 的临床治疗试剂。
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