关键词: Angiogenesis Flap IGF-PLGA Microspheres Oxidative stress

Mesh : Animals Humans Angiogenesis Angiopoietin-1 / metabolism Delayed-Action Preparations Endothelial Cells Insulin-Like Growth Factor I / pharmacology Microspheres Oxidative Stress Polylactic Acid-Polyglycolic Acid Copolymer Signal Transduction Receptor, TIE-2 / drug effects metabolism Human Umbilical Vein Endothelial Cells / drug effects metabolism

来  源:   DOI:10.1016/j.ejps.2023.106687

Abstract:
Random flaps are widely used in the treatment of injuries, tumors, congenital malformations, and other diseases. However, postoperative skin flaps are prone to ischemic necrosis, leading to surgical failure. Insulin-like growth factor- 1(IGF-1) belongs to the IGF family and exerts its growth-promoting effects in various tissues through autocrine or paracrine mechanisms. Its application in skin flaps and other traumatic diseases is relatively limited. Poly (lactic-co-glycolic acid) (PLGA) is a degradable high-molecular-weight organic compound commonly used in biomaterials. This study prepared IGF-PLGA sustained-release microspheres to explore their impact on the survival rate of flaps both in vitro and in vivo, as well as the mechanisms involved. The research results demonstrate that IGF-PLGA has a good sustained-release effect. At the cellular level, it can promote 3T3 cell proliferation by inhibiting oxidative stress, inhibit apoptosis, and enhance the tube formation ability of human umbilical vein endothelial cells (HUVEC) . At the animal level, it accelerates flap healing by promoting vascularization through the inhibition of oxidative stress. Furthermore, this study reveals the role of IGF-PLGA in activating the Angiopoietin-1(Ang1)/Tie2 signaling pathway in promoting flap vascularization, providing a strong theoretical basis and therapeutic target for the application of IGF-1 in flaps and other traumatic diseases.
摘要:
随机皮瓣广泛应用于损伤的治疗,肿瘤,先天性畸形,和其他疾病。然而,术后皮瓣易发生缺血性坏死,导致手术失败.胰岛素样生长因子-1(IGF-1)属于IGF家族,通过自分泌或旁分泌机制在各种组织中发挥其生长促进作用。其在皮瓣和其他创伤性疾病中的应用相对有限。聚(乳酸-羟基乙酸共聚物)(PLGA)是一种可降解的高分子量有机化合物,常用于生物材料中。本研究制备IGF-PLGA缓释微球,探讨其对皮瓣成活率的影响,以及所涉及的机制。研究结果表明,IGF-PLGA具有良好的缓释作用。在细胞层面,它可以通过抑制氧化应激促进3T3细胞增殖,抑制细胞凋亡,增强人脐静脉内皮细胞(HUVEC)的成管能力。在动物层面,它通过抑制氧化应激促进血管形成来加速皮瓣愈合。此外,这项研究揭示了IGF-PLGA在激活血管生成素-1(Ang1)/Tie2信号通路促进皮瓣血管形成中的作用,为IGF-1在皮瓣等创伤性疾病中的应用提供了有力的理论依据和治疗靶点。
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