Effects of cyclooxygenase-2 on sinusoidal capillarization in cirrhotic rats induced by carbon tetrachloride / 中华消化杂志

ABSTRACT

Objective To investigate the role of cyclooxygenase-2 (COX-2) in sinusoidal capillarization in liver cirrhotic rats. Methods The SD rats were intraperitoneally injected with carbon tetrachloride (CCl4) twice a week for 8 weeks to induce liver cirrhosis. The rats were randomly divided into three groups normal control group (n= 10), model control group (n= 15) and rofecoxib treated group (received 10 mg/kg of rofecoxib daily, n = 15). Liver histopathology was examined by light microscopy, and sinusoidal ultrastructure was observed by transmission electron microscopy. Furthermore, the level of basement membrane proteins (collagen type Ⅳ, laminin) and their localizations in liver were determined by Western blotting and immunohistochemistry, respectively, and the microvessel density was detected following vWF (yon Willebrand factor) immunolabeling on liver tissue sections. Results Fibrotic areas were reduced in rofecoxib treated group compared with that in model group (30.7±8.9 vs 23.5±6.5,P<0. 05). The light and electron microscopy showed that the pathologic changes including loss or reduction in number of sinusoidal endothelial fenestrate, the accumulation of extracellular matrix in the Disse's space and development of subendothelial basal lamina (basement membrane formation) were more severe in model group than those in rofecoxib treated group. Compared with model group, administration of rofecoxib resulted in significant decrease in microvessel density (11.3 ± 1.6 vs. 6.4 ±0. 7, P<0. 01). Rofecoxib could significantly decrease the expression of type Ⅳ collagen and laminin at protein levels (3.0±0.5 and 3.0±0.5, respectively) when compared with model group (3.8±0.4 and 3.7±0. 5, respectively). Conclusion The results indicate that early administration of rofecoxib may reduce sinusoidal capillarization.