Hepatoprotective effect of apolipoprotein A4 against carbon tetrachloride induced acute liver injury through mediating hepatic antioxidant and inflammation response in mice
Hepatoprotective effect of apolipoprotein A4 against carbon tetrachloride induced acute liver injury through mediating hepatic antioxidant and inflammation response in mice
复制标题
载脂蛋白A4通过介导肝脏抗氧化和炎症反应对四氯化碳诱导的急性肝损伤发挥保肝作用
DOI：
10.1016/j.bbrc.2020.11.024
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发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Li, Zongfang
中科院分区：
文献类型：
--
作者：
Li, Xiaoming;Liu, Xiaohuan;Li, Zongfang
载脂蛋白A4(ApoA4)调节脂糖代谢，在动脉粥样硬化和结肠炎中发挥抗炎作用。本研究探讨载脂蛋白A4对四氯化碳(CCl4)诱导的小鼠急性肝损伤(ALI)的保护作用。用CCl4一次性腹腔注射诱导野生型(WT)、ApoA4基因敲除(ApoA4-KO)和ApoA4转基因(ApoA4-TG)小鼠ALI模型。采集小鼠的肝脏和血液，以评估肝功能、免疫组织学变化、免疫细胞群和细胞因子谱。ApoA4缺乏加重，ApoA4过表达通过控制抗氧化酶水平减轻CCl4所致的肝损伤。ApoA4缺失增加了单核/巨噬细胞向受损肝脏的募集，并上调了血浆IL-6、TNF-α和MCP-1的水平，但降低了IL-10和干扰素-γ的水平。ApoA4的过表达挽救了这种效应，导致单核/巨噬细胞和树突状细胞百分率降低，血液中促炎/抗炎单核细胞比例降低，血浆IL-6浓度降低，而IL-10和干扰素-γ水平升高。我们建议ApoA4作为一种潜在的新的治疗靶点来管理肝损伤。(C)2020 Elsevier Inc.保留所有权利。
Apolipoprotein A4 (ApoA4) regulates lipid and glucose metabolism and exerts anti-inflammatory effects in atherogenesis and colitis. The present study explored the presumed protective role of ApoA4 in carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice. The ALI model in wild type (WT), ApoA4 knock-out (ApoA4-KO) and ApoA4 transgenic (ApoA4-TG) mice was induced by a single intraperitoneal administration of CCl4. Liver and blood were harvested from mice to assess liver functions, immunohistological changes, immune cell populations and cytokine profiles. ApoA4 deficiency aggravated, and ApoA4 overexpression alleviated CCl4-inflicted liver damage by controlling levels of anti-oxidant enzymes. ApoA4 deletion increased the recruitment of monocytes/macrophages into the injured liver and upregulated the plasma levels of IL-6, TNF-alpha and MCP-1, but lower IL-10 and IFN-gamma. ApoA4 overexpression rescued this effect and resulted in lower percentages of monocytes/macrophages and dendritic cells, the ratio of blood pro-inflammatory to anti-inflammatory monocytes and reduced plasma concentrations of IL-6, but enhanced IL-10 and IFN-gamma. We propose ApoA4 as a potential new therapeutic target for the management of liver damage. (C) 2020 Elsevier Inc. All rights reserved.