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用于减轻酒精性肝损伤的肝细胞和线粒体双靶向虾青素-乳清蛋白分离物-大豆浓缩蛋白纳米粒

Hepatocytes and mitochondria dual-targeted astaxanthin WPI-SCP nanoparticles for the alleviation of alcoholic liver injury.

作者信息

Lv Yueqi, Hao Sijia, Wang Yuxiao, Xing Shanghua, Tan Mingqian

机构信息

State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, Liaoning, China; Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, Liaoning, China; National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, Liaoning, China; Dalian Key Laboratory for Precision Nutrition, Dalian Polytechnic University, Dalian 116034, Liaoning, China; Dalian Jinshiwan Laboratory, Dalian 116034, Liaoning, China.

State Key Laboratory of Marine Food Processing and Safety Control, Dalian Polytechnic University, Dalian 116034, Liaoning, China; Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, Liaoning, China; National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, Liaoning, China; Dalian Key Laboratory for Precision Nutrition, Dalian Polytechnic University, Dalian 116034, Liaoning, China; Dalian Jinshiwan Laboratory, Dalian 116034, Liaoning, China.

出版信息

Int J Biol Macromol. 2025 Jan;285:137992. doi: 10.1016/j.ijbiomac.2024.137992. Epub 2024 Nov 22.

Abstract

Alcoholic liver injury is one of the most frequent liver diseases around the world, and nutritional intervention has been considered as an effective way to alleviate alcohol liver injury. To alleviate the liver damage caused by alcohol, a type of astaxanthin (AXT) loaded nanoparticles were designed for dual targeting of hepatocytes and mitochondria. Firstly, galactooligosaccharides (GOS) were conjugated to whey protein isolate (WPI) and sea cucumber peptide (SCP) via the Maillard reaction, achieving a grafting degree of 29 %, then triphenylphosphonium (TPP) was linked by amide reaction. Secondly, AXT was loaded into the complex of SCP-WPI-GOS-TPP (SWGT) to form AXT@SCP-WPI-GOS-TPP(AXT@SWGT) nanoparticles. The Pearson coefficient increased from 0.69 to 0.76 after introducing TPP targeting moiety. In vivo experiments showed that AXT@SWGT significantly alleviated liver injury caused by alcohol. The vacuolation and fat accumulation associated with alcoholic liver injury was alleviated. The alcohol dehydrogenase and aldehyde dehydrogenase activity were improved by 296.88 % and 34.19 %, respectively. AXT@SWGT significantly enhanced the biological activities of glutathione by 76.86 %, catalase by 145.42 %, and superoxide dismutase by 33.48 %, thereby alleviating oxidative stress. The results indicated that the AXT@SWGT might have the potential to intervene alcoholic liver injury via the dual targeting strategy.

摘要

酒精性肝损伤是全球最常见的肝脏疾病之一,营养干预被认为是减轻酒精性肝损伤的有效方法。为了减轻酒精引起的肝脏损伤,设计了一种负载虾青素(AXT)的纳米颗粒,用于对肝细胞和线粒体进行双重靶向。首先,通过美拉德反应将低聚半乳糖(GOS)与乳清分离蛋白(WPI)和海参肽(SCP)偶联,接枝度达到29%,然后通过酰胺反应连接三苯基膦(TPP)。其次,将AXT负载到SCP-WPI-GOS-TPP(SWGT)复合物中,形成AXT@SCP-WPI-GOS-TPP(AXT@SWGT)纳米颗粒。引入TPP靶向部分后,皮尔逊系数从0.69增加到0.76。体内实验表明,AXT@SWGT显著减轻了酒精引起的肝损伤。与酒精性肝损伤相关的空泡化和脂肪堆积得到缓解。乙醇脱氢酶和乙醛脱氢酶活性分别提高了296.88%和34.19%。AXT@SWGT显著提高了谷胱甘肽的生物活性76.86%、过氧化氢酶的生物活性145.42%和超氧化物歧化酶的生物活性33.48%,从而减轻了氧化应激。结果表明,AXT@SWGT可能具有通过双重靶向策略干预酒精性肝损伤的潜力。

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