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重组高密度脂蛋白对缺氧下人肩袖成纤维细胞的保护和再生作用:一项体外研究

Protective and Regenerative Effects of Reconstituted HDL on Human Rotator Cuff Fibroblasts under Hypoxia: An In Vitro Study.

作者信息

Kim Ra Jeong, Park Hyung Bin

机构信息

Institute of Medical Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea.

Department of Orthopaedic Surgery, School of Medicine, Gyengsang National University, Jinju 52727, Republic of Korea.

出版信息

Antioxidants (Basel). 2024 Apr 22;13(4):497. doi: 10.3390/antiox13040497.

Abstract

Hypoxia and hypo-high-density lipoproteinemia (hypo-HDLemia) are proposed risk factors for rotator cuff tear. HDL is recognized for its potential benefits in ischemia-driven angiogenesis and wound healing. Nevertheless, research on the potential benefits of reconstituted HDL (rHDL) on human rotator cuff fibroblasts (RCFs) under hypoxia is limited. This study investigates the cytoprotective and regenerative effects of rHDL, as well as N-acetylcysteine (NAC), vitamin C (Vit C), and HDL on human RCFs under hypoxic conditions. Sixth-passage human RCFs were divided into normoxia, hypoxia, and hypoxia groups pretreated with antioxidants (NAC, Vit C, rHDL, HDL). Hypoxia was induced by 1000 µM CoCl. In the hypoxia group compared to the normoxia group, there were significant increases in hypoxia-inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1), and Bcl-2/E1B-19kDa interacting protein 3 (BNIP3) expressions, along with reduced cell viability, elevated reactive oxygen species (ROS) production, apoptosis rate, expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase-1 (PARP-1), vascular endothelial growth factors (VEGF), and matrix metalloproteinase-2 (MMP-2), as well as decreased collagen I and III production, and markedly lower cell proliferative activity ( ≤ 0.039). These responses were significantly mitigated by pretreatment with rHDL ( ≤ 0.046). This study suggests that rHDL can enhance cell proliferation and collagen I and III production while reducing apoptosis in human RCFs under hypoxic conditions.

摘要

缺氧和低高密度脂蛋白血症(低HDL血症)被认为是肩袖撕裂的危险因素。HDL因其在缺血驱动的血管生成和伤口愈合中的潜在益处而受到认可。然而,关于重组HDL(rHDL)在缺氧条件下对人肩袖成纤维细胞(RCF)潜在益处的研究有限。本研究调查了rHDL以及N-乙酰半胱氨酸(NAC)、维生素C(Vit C)和HDL在缺氧条件下对人RCF的细胞保护和再生作用。将第六代人RCF分为常氧组、缺氧组以及用抗氧化剂(NAC、Vit C、rHDL、HDL)预处理的缺氧组。用1000µM氯化钴诱导缺氧。与常氧组相比,缺氧组中缺氧诱导因子-1α(HIF-1α)、血红素加氧酶-1(HO-1)和Bcl-2/E1B-19kDa相互作用蛋白3(BNIP3)的表达显著增加,同时细胞活力降低、活性氧(ROS)产生增加、凋亡率升高、裂解的半胱天冬酶-3、裂解的聚ADP-核糖聚合酶-1(PARP-1)、血管内皮生长因子(VEGF)和基质金属蛋白酶-2(MMP-2)的表达增加,以及I型和III型胶原蛋白产生减少,细胞增殖活性明显降低(≤0.039)。用rHDL预处理可显著减轻这些反应(≤0.046)。本研究表明,rHDL在缺氧条件下可增强人RCF的细胞增殖以及I型和III型胶原蛋白的产生,同时减少细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8d0/11047627/a64fa98b8e0d/antioxidants-13-00497-g001.jpg

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