Molecularbiological study for the role of sinusoidal cells in pathogenesis of liver disease.

肝窦细胞在肝病发病机制中作用的分子生物学研究。

基本信息

批准号：
08407016
负责人：
ISHII Hiromasa
金额：
$ 17.41万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08407016/
关键词：
Kupffer cells Sinusoidal cells Mitochondrion NO TNF-alpha NF-kB Endotoxin Alcohol TNFα NF-kB 肝疾患接着因子カルシウム NF-κB アポトーシス

项目摘要

Aim of this study is to investigate the role of sinusoidal cells, especially Kupffer cells, on various experimental liver injuries. Oxidative stress and release of nitric oxide by Kupffer cells analyzed in relation to hepatocyte injury and apoptosis.The metabolic changes in hepatoma cells co-cultured with isolated rat Kupffer cells were investigated. NO from Kupffer cells induced mitochondrial dysfunction in tumor cells followed by membrane barrier dysfunction in the liver sinusoid. Increased expression of iNOS and iNOS mRNA in the Kupffer cells co-cultured with hepatoma cells was shown. It is also suggested that CD 18/ICAM-1 dependent cell-to-cell interaction with hepatoma cells causes calcium mobilization and oxidative activation of NF-kB , which may lead to the increase production of NO in Kupffer cells. Kupffer cells stimulated by lipopolysaccharides was also shown to release NO and TNF-a, which resulted in mitochondrial injury in hepatocyte.Experimental model of alcoholic liver damage in perfused liver showed that superoxide anion was released from Kupffer cells into sinusoid by ethanol administration, and lead to damage in sinusoidal endothelial cells. Kupffer cells were shown to metabolize ethanol by cytochrome P450 2E1. After chronic ethanol feeding, LPS elicited microcirculatory disturbance with smaller dose. Expression of adhesion molecules on leukocytes, and adhesion of leukocytes in sinusoid was shown.

这项研究的目的是研究正弦细胞，尤其是库普弗细胞在各种实验性肝损伤中的作用。研究了与肝细胞损伤和凋亡相关的库普弗细胞释放一氧化氮的。研究了与分离的大鼠库普弗细胞共培养的肝癌细胞的代谢变化。 kupffer细胞中的NO诱导肿瘤细胞中的线粒体功能障碍，然后在肝正弦曲线中出现膜屏障功能障碍。显示了与肝癌细胞共培养的库普弗细胞中iNOS和iNOS mRNA的表达增加。还建议CD 18/ICAM-1依赖性细胞与细胞与肝癌细胞的相互作用会导致NF-KB的钙动员和氧化激活，这可能导致Kupffer细胞中NO的产生增加。还证明，脂多糖刺激的库普弗细胞也释放了NO和TNF-A，导致肝细胞中的线粒体损伤。灌注肝脏中酒精肝损伤的实验模型表明，超氧化物阴离子从kupffer细胞中释放出乙醇中的正弦素细胞，导致乙醇损伤，并损害源自核苷内的细胞。库普弗细胞显示通过细胞色素P450 2E1代谢乙醇。慢性乙醇进食后，LPS以较小的剂量引起微循环障碍。显示了白细胞上粘附分子的表达，并显示了正弦中白细胞的粘附。