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二十碳五烯酸对血管内皮细胞应激诱导加速衰老的保护作用。

The Protective Effects of Eicosapentaenoic Acid for Stress-induced Accelerated Senescence in Vascular Endothelial Cells.

机构信息

Department of Internal Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, South Korea.

Paik Institute for Clinical Research, Inje University, Busan, South Korea.

出版信息

Int J Med Sci. 2023 Sep 11;20(11):1479-1491. doi: 10.7150/ijms.85224. eCollection 2023.

Abstract

Eicosapentaenoic acid (EPA) is an omega-3 fatty acid that protects against cardiovascular diseases in patients with hypertriglyceridemia and may have pleotropic effects beyond lowering triglycerides. Many degenerative diseases, such as atherosclerosis and diabetes, are related to cellular senescence as a pathophysiological mechanism. We aimed to examine whether EPA could protect vascular endothelial cells under stress conditions against stress-induced accelerated senescence (SIAS). Cultured human umbilical vein endothelial cells (HUVECs) were exposed to HO as oxidative stress and a high glucose concentration with palmitate as a glucolipotoxic condition. Changes in cell viability, apoptosis, lactate dehydrogenase release, and cell cycle analysis were measured by cell counting kit-8 assay, annexin V/ propidium iodide staining, and enzyme-linked immunosorbent assay, respectively. EPA was applied in stress conditions. The degree of senescence was measured by senescence-associated beta-galactosidase staining and p16 staining using immunofluorescence. Apoptosis and cellular senescence-related proteins were measured by Western blotting. Cultured HUVECs under oxidative and glucolipotoxic stresses revealed accelerated senescence and increased apoptosis. These changes were markedly reversed by EPA administration, and the expressions of apoptosis and cellular senescence-related proteins were reversed by EPA treatment. EPA effectively protects HUVECs against SIAS, which may be one of its pleotrophic effects.

摘要

二十碳五烯酸(EPA)是一种ω-3 脂肪酸,可预防高甘油三酯血症患者的心血管疾病,并且除了降低甘油三酯外,可能还有多种作用。许多退行性疾病,如动脉粥样硬化和糖尿病,都与细胞衰老作为病理生理机制有关。我们旨在研究 EPA 是否可以保护血管内皮细胞在应激条件下免受应激诱导的加速衰老(SIAS)。将培养的人脐静脉内皮细胞(HUVEC)暴露于 HO 作为氧化应激和高葡萄糖浓度以及棕榈酸作为糖脂毒性条件。通过细胞计数试剂盒-8 测定、膜联蛋白 V/碘化丙啶染色和酶联免疫吸附测定分别测量细胞活力、细胞凋亡、乳酸脱氢酶释放和细胞周期分析。在应激条件下应用 EPA。通过衰老相关β-半乳糖苷酶染色和免疫荧光法用 p16 染色测量衰老程度。通过 Western blot 测量细胞凋亡和与细胞衰老相关的蛋白表达。在氧化和糖脂毒性应激下培养的 HUVEC 显示出加速衰老和增加的细胞凋亡。这些变化通过 EPA 给药明显逆转,并且通过 EPA 处理逆转了细胞凋亡和与细胞衰老相关的蛋白表达。EPA 可有效保护 HUVEC 免受 SIAS 的侵害,这可能是其多种作用之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb58/10542193/0a58ead0b066/ijmsv20p1479g001.jpg

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