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贝伐单抗干预实验性视网膜中央静脉阻塞的蛋白质组学分析

Proteome Analysis of Bevacizumab Intervention in Experimental Central Retinal Vein Occlusion.

作者信息

Cehofski Lasse Jørgensen, Kruse Anders, Mæng Mads Odgaard, Kjaergaard Benedict, Grauslund Jakob, Honoré Bent, Vorum Henrik

机构信息

Department of Ophthalmology, Odense University Hospital, 5000 Odense, Denmark.

Biomedical Research Laboratory, Aalborg University Hospital, 9000 Aalborg, Denmark.

出版信息

J Pers Med. 2023 Nov 7;13(11):1580. doi: 10.3390/jpm13111580.

Abstract

Bevacizumab is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the management of macular edema in central retinal vein occlusion (CRVO). Studying retinal protein changes in bevacizumab intervention may provide insights into mechanisms of action. In nine Danish Landrace pigs, experimental CRVO was induced in both eyes with argon laser. The right eyes received an intravitreal injection of 0.05 mL bevacizumab (n = 9), while the left control eyes received 0.05 mL saline water (NaCl). Retinal samples were collected 15 days after induced CRVO. Label-free quantification nano-liquid chromatography-tandem mass spectrometry identified 59 proteins that were regulated following bevacizumab treatment. Following bevacizumab intervention, altered levels of bevacizumab components, including the Ig gamma-1 chain C region and the Ig kappa chain C region, were observed. Changes in other significantly regulated proteins ranged between 0.58-1.73, including for the NADH-ubiquinone oxidoreductase chain (fold change = 1.73), protein-transport protein Sec24B (fold change = 1.71), glycerol kinase (fold change = 1.61), guanine-nucleotide-binding protein G(T) subunit-gamma-T1 (fold change = 0.67), and prefoldin subunit 6 (fold change = 0.58). A high retinal concentration of bevacizumab was achieved within 15 days. Changes in the additional proteins were limited, suggesting a narrow mechanism of action.

摘要

贝伐单抗是治疗视网膜中央静脉阻塞(CRVO)所致黄斑水肿时常用的血管内皮生长因子(VEGF)抑制剂。研究贝伐单抗干预后的视网膜蛋白变化可能有助于深入了解其作用机制。在9只丹麦长白猪中,双眼用氩激光诱导实验性CRVO。右眼玻璃体内注射0.05 mL贝伐单抗(n = 9),而左眼作为对照注射0.05 mL盐水(NaCl)。在诱导CRVO后15天采集视网膜样本。无标记定量纳米液相色谱-串联质谱法鉴定出59种在贝伐单抗治疗后受到调控的蛋白质。贝伐单抗干预后,观察到其成分水平发生改变,包括Igγ-1链C区和Igκ链C区。其他显著调控蛋白的变化范围在0.58 - 1.73之间,包括NADH-泛醌氧化还原酶链(倍数变化 = 1.73)、蛋白质转运蛋白Sec24B(倍数变化 = 1.71)、甘油激酶(倍数变化 = 1.61)、鸟嘌呤核苷酸结合蛋白G(T)亚基γ-T1(倍数变化 = 0.67)和前折叠蛋白亚基6(倍数变化 = 0.58)。在15天内视网膜达到了较高的贝伐单抗浓度。其他蛋白质的变化有限,提示其作用机制较为狭窄。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6554/10672637/76e4bd41d1da/jpm-13-01580-g001.jpg

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