Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis

• Published in: PloS one 2013-07, Vol.8 (7), p.e69309-e69309
• Main Authors: Gao, Jin-Hang, Wen, Shi-Lei, Yang, Wen-Juan, Lu, Yao-Yao, Tong, Huan, Huang, Zhi-Yin, Liu, Zhang-Xu, Tang, Cheng-Wei
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Arthritis; Bile; Biology; Blood flow; c-Fos protein; Casts; Catheters; Celecoxib; Cirrhosis; Collagen (type III); Cyclooxygenase-2; Disease Models, Animal; Down-regulation; Extracellular signal-regulated kinase; Fibrosis; Flow resistance; Gastroenterology; Hepatology; Hospitals; Hypertension; Hypertension, Portal - complications; Hypertension, Portal - drug therapy; Hypertension, Portal - physiopathology; Hypoxia; Hypoxia-inducible factors; Kidney - drug effects; Kidney - pathology; Kidney - physiopathology; Laboratories; Liver; Liver cancer; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - drug therapy; Liver Cirrhosis - physiopathology; Liver diseases; Male; Medical prognosis; Medicine; mRNA; Neovascularization, Pathologic - complications; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - physiopathology; Peptides; Peritoneum; Portal vein; Prostaglandin E2; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Rats; Rats, Sprague-Dawley; Rodents; Signal Transduction - drug effects; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; Thioacetamide; Vascular endothelial growth factor; Vascular endothelial growth factor receptors; Veterinary Science
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069309

Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated. Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p