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整合蛋白质组学和代谢组学以阐明L-茶氨酸减轻小鼠异丙肾上腺素诱导的心脏损伤的基本有益机制。

Integrated proteomics and metabolomics to clarify the essential beneficial mechanisms of L-theanine in alleviating ISO-induced cardiac damage in mice.

作者信息

Wang Guoping, Zhang Luwen, Li Wei, Liu Xingxing, Huang Jichang

机构信息

Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, Chengdu, Sichuan, China.

Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, Chengdu, Sichuan, China; School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, China.

出版信息

Food Res Int. 2025 May;209:116235. doi: 10.1016/j.foodres.2025.116235. Epub 2025 Mar 22.

DOI:10.1016/j.foodres.2025.116235
PMID:40253182
Abstract

L-theanine (L-Thea), a bioactive amino acid found in tea, demonstrates remarkable nutraceutical properties. Isoproterenol (ISO) has been utilized as a reliable and potent agent to induce heart failure (HF) in murine models. The aim of this study was to explore the mechanisms through which L-Thea alleviates ISO-induced cardiac damage via the examination of proteomic and metabolomic data. Herein, we first successfully developed an ISO-induced cardiac injury model in mice. Then, the intervention with L-Thea demonstrated an improvement in cardiac performance and enhanced ventricular function. The results of histological assessments suggested that L-Thea has the potential to mitigate inflammatory infiltration, cardiomyocytes loss, and myocardial fibrosis in heart tissue affected by ISO-induced cardiac injuries in mice. Moreover, the proteomic data indicated that L-Thea led to a significant reduction in apoptosis, the p53 signaling pathway, and the IL-17 signaling pathway within cardiac tissue. Significantly, there were five KEGG pathways that were shown in both the proteome and metabolome, including apoptosis, purine metabolism, cAMP signaling pathway, ABC transporters and cytochrome P450. The western blot results further confirmed that L-Thea induced the downregulation of BAX (pro-apoptotic protein) and the upregulation of BCL-2 (anti-apoptotic protein), thereby suppressing apoptosis in the cardiac tissue of mice. Collectively, L-Thea possesses the capacity to function as a dietary supplement for the prevention or management of cardiac damage induced by ISO.

摘要

L-茶氨酸(L-Thea)是一种存在于茶叶中的生物活性氨基酸,具有显著的营养保健特性。异丙肾上腺素(ISO)已被用作在小鼠模型中诱导心力衰竭(HF)的可靠且有效的药物。本研究的目的是通过检查蛋白质组学和代谢组学数据,探索L-茶氨酸减轻ISO诱导的心脏损伤的机制。在此,我们首先成功建立了小鼠ISO诱导的心脏损伤模型。然后,用L-茶氨酸进行干预显示心脏功能得到改善,心室功能增强。组织学评估结果表明,L-茶氨酸有可能减轻小鼠ISO诱导的心脏损伤所影响的心脏组织中的炎症浸润、心肌细胞损失和心肌纤维化。此外,蛋白质组学数据表明,L-茶氨酸导致心脏组织中的细胞凋亡、p53信号通路和IL-17信号通路显著减少。值得注意的是,蛋白质组和代谢组中都显示出五条KEGG通路,包括细胞凋亡、嘌呤代谢、cAMP信号通路、ABC转运蛋白和细胞色素P450。蛋白质印迹结果进一步证实,L-茶氨酸诱导促凋亡蛋白BAX的下调和抗凋亡蛋白BCL-2的上调,从而抑制小鼠心脏组织中的细胞凋亡。总体而言,L-茶氨酸有能力作为一种膳食补充剂,用于预防或管理由ISO诱导的心脏损伤。

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引用本文的文献

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