Department of Medical Education, Center for Anatomy and Functional Morphology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Anat Rec (Hoboken). 2022 Jul;305(7):1592-1610. doi: 10.1002/ar.24829. Epub 2021 Nov 23.
This article reviews the literature on capillarization of hepatic sinusoids since its discovery in 1963. Liver sinusoidal endothelial cells are uniquely fenestrated and lack an underlying basement membrane. In chronic liver disease, the sinusoids capillarize and transform into systemic capillaries, a process termed capillarization of sinusoids. The histopathology is marked by defenestration, basement membrane formation, and space of Disse fibrogenesis. Capillarized sinusoids compromise the bidirectional exchange of materials between sinusoids and hepatocytes, leading to hepatocellular dysfunction. Sinusoidal capillarization was first described in active cirrhosis of alcoholics in 1963. Since then, it has been found in early and progressive stages of alcoholic hepatic fibrosis before the onset of cirrhosis. The sinusoidal structure is not altered in alcoholic steatosis without fibrosis. Defenestration impairs the ability of the endothelium to filter chylomicron remnants from sinusoids into the Disse's space, contributing to alcohol-induced postprandial hyperlipidemia and possibly atherosclerosis. Ethanol also modulates the fenestration dynamics in animals. In baboons, chronic alcohol consumption diminishes endothelial porosity in concomitance with hepatic fibrogenesis and in rats defenestrates the endothelium in the absence of fibrosis, and sometimes capillarizes the sinusoids. Acute ethanol ingestion enlarges fenestrations in rats and contracts fenestrations in rabbits. In sinusoidal endothelial cell culture, ethanol elicits fenestration dilation, which is likely related to its interaction with fenestration-associated cytoskeleton. Ethanol potentiates sinusoidal injury caused by cocaine, acetaminophen or lipopolysaccharide in mice and rats. Understanding ethanol's mechanisms on pathogenesis of sinusoidal capillarization and fenestration dynamics will lead to development of methods to prevent risks for atherosclerosis in alcoholism.
本文回顾了自 1963 年发现肝窦毛细血管化以来的相关文献。肝窦内皮细胞具有独特的窗孔结构，且缺乏基底膜。在慢性肝病中，窦状隙发生毛细血管化并转变为全身毛细血管，这一过程称为窦状隙毛细血管化。其组织病理学特征为窗孔缺失、基底膜形成和 Disse 空间纤维生成。毛细血管化的窦状隙会影响窦状隙和肝细胞之间物质的双向交换，导致肝细胞功能障碍。窦状隙毛细血管化最早于 1963 年在酒精性活动期肝硬化中被描述。此后，在肝硬化发生之前，在酒精性肝纤维化的早期和进展期就已发现这种现象。无纤维化的酒精性脂肪变性不会改变窦状隙结构。窗孔缺失会损害内皮细胞将乳糜微粒残片从窦状隙过滤到 Disse 空间的能力，导致酒精引起的餐后高脂血症，并可能导致动脉粥样硬化。乙醇还可调节动物窦状隙的窗孔动力学。在狒狒中，慢性酒精摄入会伴随着肝纤维化而降低内皮通透性，而在大鼠中，在没有纤维化的情况下内皮会出现窗孔缺失，有时窦状隙也会发生毛细血管化。急性乙醇摄入会扩大大鼠的窗孔，并缩小兔的窗孔。在窦内皮细胞培养中，乙醇会引起窗孔扩张，这可能与其与窗孔相关的细胞骨架相互作用有关。乙醇会增强可卡因、对乙酰氨基酚或脂多糖在小鼠和大鼠中引起的窦状隙损伤。了解乙醇在窦状隙毛细血管化和窗孔动力学发病机制中的作用机制，将有助于开发预防酒精中毒性动脉粥样硬化风险的方法。
