Study on the mechanisms of development of hepatic sinusoidal capillarization / 中华消化杂志

ABSTRACT

Objective To study the relationship between the liver sinusoidal pathological changes and portal hypertension during the dimethylnitrosamine (DMN) induced liver fibrosis in rats. Methods The rat liver fibrosis model was established by peritoneal injection of DMN (at a dose of 10 mg/kg, 3 times a week, for 4 weeks) in 40 male Wister mice. In the control group of 24 healthy mice, saline solution was injected peritoneally. The dynamic changes of liver fibrosis were observed at different time points (1, 2, 3 day, 1, 2, 4, 6 and 8 week). The pressure of portal vein (Ppv) was directly measured by the intubation of mesentery anterior vein in 5 mice of the model and 3 of the control. The expressions of type Ⅳ collagen (Col Ⅳ), laminin (LM) and type Ⅰ collagen (Col Ⅰ) were detected by immunohistochemistry. Hepatic ultrastructure was observed by electron microscopy. Results Positive expression of Col Ⅳ was observed in the normal liver sinusoidal walls. The various intensities of positive staining of Col Ⅳ were observed in the liver sinusoidal walls of the fibrosis model. Positive expressions of LM and Col Ⅰ increased, and the strongest positive staining displayed in the 4 week model rats. Meanwhile, the fenestrae in the sinusoidal endothelial cells (SECs) were lost and the basal membrane was formed. There was a remarkable positive correlation between the Ppv and the expressions of LM in the DMN induced rat fibrosis( P