Oda Masaya, Yokomori Hiroaki, Han Jing-Yan
Organized Center of Clinical Medicine, International University of Health & Welfare and Department of Internal Medicine, Sanno Hospital, Tokyo 107-0052, Japan.
Clin Hemorheol Microcirc. 2003;29(3-4):167-82.
Hepatic microvasculature receives blood from two types of afferent vessels: the terminal portal venule (TPVn) and the terminal hepatic arteriole (THAo). The TPVns directly connect with the capillary bed in the liver parenchyma, which is referred to as sinusoids. Hepatic arterial blood pours into the hepatic sinusoids not only indirectly via the anastomosis between the THAo and the portal venule (PVn), but also directly through the THAo or the capillaries derived from the arterial capillary network around the bile duct. From a regulatory point of view, the hepatic arterial system is considered to be supplementary, but hepatic arterial flow is essential for supplying oxygen to sinusoidal blood flow as well as to the bile ducts, portal venules and nerves in the portal tract. The main regulators of hepatic sinusoidal blood flow are present in the portal venous system. By intravital and scanning electron microscopy, it is evident that a potent vasoconstrictor endothelin (ET)-1 causes a contraction of the SEF via the ET_B receptors, as well as a significant contraction of the PVn and TPVn, resulting in an increase in sinusoidal and pre-sinusoidal microvascular resistance. This phenomenon implies that the TPVn, particularly the transitional part to the sinusoid, would provide an essential regulatory site for hepatic sinusoidal blood flow as an inlet sphincter-like function. The endothelial cell linings along the hepatic sinusoids are characterized by the presence of a large number of sieve plate-like pores, 100 nm in diameter, i.e. the sinusoidal endothelial fenestrae (SEF). The SEF are dynamic structures, forming the racemose invaginations of the endothelial plasma membrane across the endothelium, and regulating not only the permeability of hepatic sinusoids, but also the sinusoidal blood flow by the Ca++ -actomyosin-mediated contraction and dilatation of the SEF. Our recent immunoelectron microscopic and Western blot studies have revealed that caveolin-1, i.e. the principal structural protein of caveolae, and endothelial nitric oxide synthase (eNOS) co-exist in the plasma membrane of the SEF, implying that the SEF may correspond to a permanent (stationary) type of fused and interconnected caveolae, thus contributing to the local control of hepatic sinusoidal blood flow by the regulation of NO synthesis.
终末门静脉小支（TPVn）和终末肝小动脉（THAo）。TPVn直接与肝实质中的毛细血管床相连，该毛细血管床被称为肝血窦。肝动脉血不仅通过THAo与门静脉小支（PVn）之间的吻合间接流入肝血窦，还可直接通过THAo或源自胆管周围动脉毛细血管网的毛细血管流入。从调节角度来看，肝动脉系统被认为是辅助性的，但肝动脉血流对于向肝血窦血流以及胆管、门静脉小支和门管区的神经供应氧气至关重要。肝血窦血流的主要调节因子存在于门静脉系统中。通过活体显微镜和扫描电子显微镜观察发现，一种强效血管收缩剂内皮素（ET）-1通过ET_B受体引起肝血窦内皮窗孔（SEF）收缩，以及PVn和TPVn的显著收缩，导致血窦和血窦前微血管阻力增加。这种现象表明，TPVn，特别是与血窦相连的过渡部分，作为类似入口括约肌的功能，可能为肝血窦血流提供一个重要的调节位点。沿肝血窦的内皮细胞内衬的特征是存在大量直径为100纳米的筛板样小孔，即血窦内皮窗孔（SEF）。SEF是动态结构，形成横跨内皮的内皮细胞质膜的葡萄状内陷，不仅调节肝血窦的通透性，还通过Ca++ - 肌动球蛋白介导的SEF收缩和舒张来调节血窦血流。我们最近的免疫电子显微镜和蛋白质印迹研究表明，小窝蛋白-1（即小窝的主要结构蛋白）和内皮型一氧化氮合酶（eNOS）共存于SEF的质膜中，这意味着SEF可能对应于一种永久（固定）类型的融合且相互连接的小窝，从而通过调节NO合成来参与肝血窦血流的局部控制。
