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赖氨酸补充剂可减轻慢性小鼠实验性自身免疫性肝炎。

L-lysine supplementation attenuates experimental autoimmune hepatitis in a chronic murine model.

机构信息

Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, P.R. China.

Department of Gastroenterology, Shangrao People's Hospital, Shangrao 334000, Jiangxi Province, P.R. China.

出版信息

Exp Anim. 2024 Feb 14;73(1):83-92. doi: 10.1538/expanim.23-0053. Epub 2023 Aug 31.

Abstract

The incidence of autoimmune hepatitis (AIH) has increased significantly worldwide. The present study aims to explore the protective effect of L-lysine supplementation against AIH and to investigate its potential underlying mechanisms. A chronic experimental AIH mouse model was established by repeated tail vein injection of human cytochrome P450 2D6 (CYP2D6) plasmid. Starting from day 14 of the modeling, mice in the CYP2D6-AIH +L-lysine group were given 200 µl of purified water containing 10 mg/kg L-lysine by gavage until day27, once a day, and mice in the healthy control group and model group were given an equal volume of purified water by gavage. Our results showed that L-lysine supplementation partially reversed the liver injury mediated by CYP2D6 overexpression. These effects were consistent with the restraining impacts of L-lysine supplementation on decreasing pro-inflammatory cytokines expression level and CD4 and CD8 T lymphocytes infiltration, as well as curbing hepatic oxidative stress. Furthermore, L-lysine supplement relieved liver fibrosis in the context of AIH. In conclusion, L-lysine supplementation attenuates CYP2D6-induced immune liver injury in mice, which may serve as a novel nutrition support approach for AIH.

摘要

自身免疫性肝炎 (AIH) 的发病率在全球范围内显著增加。本研究旨在探讨 L-赖氨酸补充对 AIH 的保护作用,并探讨其潜在的机制。通过反复尾静脉注射人细胞色素 P450 2D6 (CYP2D6) 质粒建立慢性实验性 AIH 小鼠模型。从建模的第 14 天开始,CYP2D6-AIH+L-赖氨酸组的小鼠通过灌胃给予含有 10mg/kg L-赖氨酸的 200µl 纯化水,每天一次,而健康对照组和模型组的小鼠通过灌胃给予等量的纯化水。我们的结果表明,L-赖氨酸补充部分逆转了 CYP2D6 过表达介导的肝损伤。这些作用与 L-赖氨酸补充通过降低促炎细胞因子表达水平和 CD4 和 CD8 T 淋巴细胞浸润以及抑制肝氧化应激来抑制免疫反应的作用一致。此外,L-赖氨酸补充减轻了 AIH 背景下的肝纤维化。总之,L-赖氨酸补充可减轻 CYP2D6 诱导的小鼠免疫性肝损伤,可为 AIH 提供一种新的营养支持方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/891e/10877156/3e9877014e6c/expanim-73-083-g001.jpg

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