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Roles of low molecular ononoxides in regulation of hepatobiliary function

低分子氧化氮在肝胆功能调节中的作用

基本信息

批准号：
06454264
负责人：
SUEMATSU Makoto
金额：
$ 4.61万
依托单位：
Keio University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454264/
关键词：
carbon monoxide nitric oxide heme oxygenase microcirculation Ito cell liver cholestasis bilirubin heme oxygenase 一酸化窒素ラジカル cGMP 肝類洞循環

项目摘要

Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to monitor sinusoidal lining and fat-storing Ito cells, alternately. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min /g liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 muM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity. The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cells which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 muM) or a cGMP analogue 8-bromo-cGMP (1 muM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells.

血红素加氧酶是一种血红素氧化酶，能产生胆绿素和一氧化碳。本研究的目的是阐明是否CO内源性产生的这种酶作为一个积极的血管舒张剂在肝微循环。通过双色数字显微荧光成像技术观察离体灌注大鼠肝脏的微血管，交替监测肝窦内衬和脂肪储存Ito细胞。在对照肝脏中，静脉流出物中的CO通量范围为0.7 nmol/min /g肝脏。血红素加氧酶抑制剂锌原卟啉IX（1 μ M）的给药消除了基线CO生成，并且血管阻力显示出30%的升高，同时伴有离散的窦状隙收缩模式和窦状隙灌注速度的降低。收缩的主要部位对应于与Ito细胞共定位的局部正弦段，其通过成像其维生素A自体荧光来识别。在灌注液中加入CO（1 μ M）或cGMP类似物8-溴-cGMP（1 μ M）可显著减弱血管阻力和窦状收缩的增加。从这些发现，我们建议，CO可以作为一个内源性调制器的肝窦灌注通过放松机制，涉及伊藤细胞。