Yokomori H, Oda M, Ogi M, Kamegaya Y, Tsukada N, Nakamura M, Ishii H
Department of Internal Medicine, Kitasato, Medical Center Hospital, Saitama, Tokyo, Japan.
Liver. 2001 Apr;21(2):114-22. doi: 10.1034/j.1600-0676.2001.021002114.x.
BACKGROUND/AIMS: A number of vasoactive substances have been implicated as potential mediators of intrahepatic portal hypertension. Endothelin (ET)-1 has been suggested to be involved in the regulation of hepatic microcirculation and development of portal hypertension. The aim of this study was to clarify the localization of two subtypes of ET receptors, ET A (ETAR) and B receptors (ETBR), in normal rat liver, and how the receptor expressions are altered in CCl4-induced cirrhotic rat liver.
Liver specimens were examined immunohistochemically after reacting with anti-ETAR and anti-ETBR rabbit polyclonal antibodies. Immunogold staining was also performed using the same antibodies, and examined under light and electron microscopy.
In normal rat liver, immunohistochemistry revealed expression of ETAR and ETBR on the hepatic sinusoidal lining cells. By immunogold electron microscopy, electron-dense gold particles indicating the presence of ETARs were localized mainly on hepatic stellate cells (HSCs) and to a lesser extent on sinusoidal endothelial cells (SECs), while ETBRs were expressed equally intensely on HSCs and SECs. In cirrhotic animals, both ETAR and ETBR increased significantly on HSCs, while there were no significant increases in either receptor on SECs.
In the normal state, HSCs possess both ETARs and ETBRs, while SECs mainly possess ETBRs. In cirrhosis, endothelins may exert more intense effects on HSCs via the enhanced ETARs and ETBRs, causing an increase in hepatic sinusoidal microvascular tone.
背景/目的：多种血管活性物质被认为是肝内门静脉高压的潜在介质。内皮素（ET）-1被认为参与肝微循环的调节和门静脉高压的发展。本研究的目的是阐明ET受体的两种亚型，即ET A（ETAR）和B受体（ETBR）在正常大鼠肝脏中的定位，以及在四氯化碳诱导的肝硬化大鼠肝脏中受体表达如何改变。
肝脏标本与抗ETAR和抗ETBR兔多克隆抗体反应后进行免疫组织化学检查。也使用相同的抗体进行免疫金染色，并在光镜和电镜下检查。
在正常大鼠肝脏中，免疫组织化学显示ETAR和ETBR在肝窦内衬细胞上表达。通过免疫金电子显微镜观察，表明存在ETAR的电子致密金颗粒主要定位于肝星状细胞（HSC），在较小程度上定位于窦内皮细胞（SEC），而ETBR在HSC和SEC上的表达强度相同。在肝硬化动物中，HSC上的ETAR和ETBR均显著增加，而SEC上的两种受体均无显著增加。
在正常状态下，HSC同时具有ETAR和ETBR，而SEC主要具有ETBR。在肝硬化时，内皮素可能通过增强的ETAR和ETBR对HSC发挥更强的作用，导致肝窦微血管张力增加。
