肠道来源的高密度脂蛋白通过门静脉抑制肝损伤，这一成果由美国华盛顿大学Gwendalyn J. Randolph、Yong-Hyun Han等研究人员合作完成。该研究于2021年7月23日发表于国际一流学术期刊《科学》。
研究人员表明，肠道来源的高密度脂蛋白以HDL3亚种形式穿越门静脉，与脂多糖（LPS）结合蛋白（LBP）复合。HDL3，而不是HDL2或低密度脂蛋白，阻止了LPS与肝脏巨噬细胞的结合和炎症激活，并促进LPS的细胞外失活。在涉及手术、饮食或酒精性肠道损伤的小鼠模型中，肠道来源的高密度脂蛋白的损失使肝脏损伤恶化，而通过提高和依赖提高肠道高密度脂蛋白的治疗方法，结果得到改善。因此，保护肝脏免受来自肠道LPS的伤害是肠道合成HDL的一个主要功能。
据研究人员介绍，高密度脂蛋白的生物生成需要apoA1和胆固醇转运体ABCA1。尽管肝脏产生了血液中的大部分高密度脂蛋白，但高密度脂蛋白的合成也发生在小肠中。
附：英文原文
Title: Enterically derived high-density lipoprotein restrains liver injury through the portal vein
Author: Yong-Hyun Han, Emily J. Onufer, Li-Hao Huang, Robert W. Sprung, W. Sean Davidson, Rafael S. Czepielewski, Mary Wohltmann, Mary G. Sorci-Thomas, Brad W. Warner, Gwendalyn J. Randolph
Issue&Volume: 2021/07/23
Abstract: The biogenesis of high-density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most of the HDL in the blood, HDL synthesis also occurs in the small intestine. Here, we show that intestine-derived HDL traverses the portal vein in the HDL3 subspecies form, in complex with lipopolysaccharide (LPS)–binding protein (LBP). HDL3, but not HDL2 or low-density lipoprotein, prevented LPS binding to and inflammatory activation of liver macrophages and instead supported extracellular inactivation of LPS. In mouse models involving surgical, dietary, or alcoholic intestinal insult, loss of intestine-derived HDL worsened liver injury, whereas outcomes were improved by therapeutics that elevated and depended upon raising intestinal HDL. Thus, protection of the liver from injury in response to gut-derived LPS is a major function of intestinally synthesized HDL.
DOI: 10.1126/science.abe6729
Source: https://science.sciencemag.org/content/373/6553/eabe6729