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IGF-1C 结构域修饰纳米颗粒对小鼠肾缺血再灌注损伤的影响。

Effect of IGF-1C domain-modified nanoparticles on renal ischemia-reperfusion injury in mice.

机构信息

Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

出版信息

Ren Fail. 2022 Dec;44(1):1376-1387. doi: 10.1080/0886022X.2022.2098773.

Abstract

Renal ischemia-reperfusion injury (IRI) is a common prerequisite of acute renal injury (AKI) that involves the entire system and induces critical illness. The C domain of insulin-like growth factor-1 (IGF-1C) plays an important role in promoting angiogenesis and enhancing the inflammatory response. However, given the shortcomings of its short half-life and poor stability, the application of IGF-1C is restricted. In the present study, IGF-1C nanoparticles (NP-IGF-1C) were constructed by combining 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-maleimide (polye thyleneglycol) and IGF-1C through a Michael addition reaction to evaluate the effects of NP-IGF-1C on preventing IRI. studies have shown that NP-IGF-1C is not cytotoxic and protects cells from oxidative damage. The renal enrichment and biocompatibility of NP-IGF-1C were determined by connecting fluorescent molecules to NP-IGF-1C for imaging and pathological staining of important organs. After IRI, renal function decreased, and inflammatory cell infiltration, oxidative stress and apoptosis increased. As expected, NP-IGF-1C reversed these changes, indicating that NP-IGF-1C played a protective role in the process of IRI, which may be mediated by its antioxidant, anti-inflammatory and antiapoptotic activities.

摘要

肾缺血再灌注损伤 (IRI) 是急性肾损伤 (AKI) 的常见前提,涉及整个系统,并引发危急病症。胰岛素样生长因子-1 (IGF-1) 的 C 结构域在促进血管生成和增强炎症反应方面发挥着重要作用。然而,由于其半衰期短和稳定性差的缺点,IGF-1 的应用受到限制。在本研究中,通过迈克尔加成反应将胰岛素样生长因子-1 (IGF-1) 与 1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-马来酰亚胺(聚乙二醇) 结合构建 IGF-1C 纳米颗粒 (NP-IGF-1C),以评估 NP-IGF-1C 对预防 IRI 的影响。研究表明,NP-IGF-1C 无细胞毒性,可保护细胞免受氧化损伤。通过将荧光分子连接到 NP-IGF-1C 上来确定 NP-IGF-1C 的肾脏富集和生物相容性,用于 NP-IGF-1C 的重要器官成像和病理染色。IRI 后,肾功能下降,炎症细胞浸润、氧化应激和细胞凋亡增加。正如预期的那样,NP-IGF-1C 逆转了这些变化,表明 NP-IGF-1C 在 IRI 过程中发挥了保护作用,这可能是通过其抗氧化、抗炎和抗凋亡活性介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c0/9389927/5c4441ec56be/IRNF_A_2098773_F0001_C.jpg

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