[肝窦内皮细胞损伤在二甲基亚硝胺诱导大鼠肝纤维化形成中的作用]

[Role of hepatic sinusoidal endothelium injury in hepatic fibrogenesis induced by dimethylnitrosamine in rats].

作者信息

Lu Xiong, Liu Ping, Liu Chenghai, Xu Guangfu, Wang Xianbo, Chen Wenhui, Li Fenghua

机构信息

Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2002 Dec;10(6):441-4.

PMID:12502448

Abstract

OBJECTIVE

To study the role of hepatic sinusoidal endothelium injury during hepatic fibrogenesis induced by dimethylnitrosamine (DMN) in rats.

METHODS

Hepatic fibrosis of rats was induced by administration of DMN intraperitoneally three times a week for 4 weeks. The animals were harvested on day 2 and week 1, 2, 3, 4, 5, 6, 8, 12, and 24. The formation of liver fibrosis and hepatic sinusoid capillarization were successively observed by morphological observation and other methods.

RESULTS

Two days after treated with DMN, there was no obvious changes in the liver, but the fenestration of the sinusoidal endothelial cells decreased, and it became more obvious after one week. After four weeks, there was a large necrotic area and a number of pseudolobes appeared. The HA in the serum was lower than that of control (231.30 ng/ml +/- 143.80 ng/ml vs 56.50 ng/ml +/- 18.10 ng/ml; t=3.14, P<0.05), but the hydroxyproline content was obviously higher than that of control (223.04 microg/g +/- 37.09 microg/g vs 61.55 microg/g +/- 20.85 microg/g; t=8.28, P<0.05). Hepatic sinusoid capillarization was gradually formed and defenestration of the hepatic sinusoidal endothelium preceded the appearance of serious hepatocellular damage, hepatic fibrosis and basement membrane.

CONCLUSIONS

The damage and phenotypic alteration of the hepatic sinusoidal endothelium may be a vital issue triggering the liver fibrosis induced by DMN.

摘要

目的

研究肝窦内皮细胞损伤在二甲基亚硝胺（DMN）诱导的大鼠肝纤维化形成过程中的作用。

方法

每周3次腹腔注射DMN，连续4周诱导大鼠肝纤维化。分别于第2天以及第1、2、3、4、5、6、8、12和24周处死动物。通过形态学观察等方法连续观察肝纤维化形成及肝窦毛细血管化情况。

结果

DMN处理2天后，肝脏无明显变化，但肝窦内皮细胞窗孔减少，1周后更为明显。4周后，出现大片坏死区并出现大量假小叶。血清中透明质酸（HA）低于对照组（231.30 ng/ml±143.80 ng/ml比56.50 ng/ml±18.10 ng/ml；t=3.14，P<0.05），但羟脯氨酸含量明显高于对照组（223.04 μg/g±37.09 μg/g比61.55 μg/g±20.85 μg/g；t=8.28，P<0.05）。肝窦毛细血管化逐渐形成，肝窦内皮细胞窗孔消失先于严重肝细胞损伤、肝纤维化及基底膜的出现。