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.