Expression of cyclooxygenase-2 and its pathogenic effects in nonalcoholic fatty liver disease

Objective:To investigate the expression of cyclooxygenase-2 and its pathological effect in the experimental nonalcoholic fatty liver of rats,and to explore its possible mechanism.Methods:The rat NAFLD model was established by giving a fat-enriched diet.The blood samples were obtained form abdominal aorta and the levels of serum ALT,AST and IL-1,changes in the hepatic tissue 6-k-PGF1α TXB2 were measured.The expression level of COX-2 in rats livers were assayed by immunohistochemistry,RT-PCR and Western-blot.Results:Light microscope analysis revealed that hepatocytes were injured in the model group and slightly in the treatment group.The levels of serum TXB2 and IL-1 in the fatty liver rats were increased.Compared with the model group,the IL-1 and TXB2 increased significantly(P < 0.05),on the contrary,compared with the normal group,the hepatic tissue 6-Keto-prostagland decreased significantly in the model group(P < 0.05),the treatment group also increased but P > 0.05.There was no positive expression of COX-2 in hepatic tissue of normal rats.In the model group,there was positive expression of COX-2 antigen and the number of COX positive cells progressively increased at 4,8,12 wks.The intensity of expression of COX-2 had significantly increased(P < 0.05)and the intensity of COX-2 expression in the treated group decreased remarkably compared with the model group(P < 0.05).The expression of COX-2 mRNA and the level of COX-2 protein were significantly stronger in the liver of model rats compared with normal rats,and significantly weaker in treated rats,than in 8W and 12W model rats(P < 0.05).Conclusion:The increase of COX-2 expression in NAFLD is closely associated with the severity of liver inflammation and damage.COX-2 may play an important role in the progression of rat NAFLD,and the expression of COX-2 mRNA is downregulated by cyclooxygenase-2 inhibitor,which can depress the oxidative stress and control inflammatory response efficiently.

Expression of cyclooxygenase-2 and its pathogenic effects in nonalcoholic fatty liver disease

Objective:To investigate the expression of cyclooxygenase-2 and its pathological effect in the experimental nonalcoholic fatty fiver of rats, and to explore its possible mechanism. Methods:The rat NAFLD model was established by giving a fat-enriched diet. The blood samples were obtained form abdominal aorta and the levels of serum ALT, AST and IL-1, changes in the hepatic tissue 6-k-PGF1 α TXB2 were measured. The expression level of COX-2 in rats livers were assayed by immunohistochemistry, RT-PCR and Western-blot. Results: Light microscope analysis revealed that hepatocytes were injured in the model group and slightly in the treatment group. The levels of serum TXB2 and IL-1 in the fatty liver rats were increased. Compared with the model group, the IL-] and TXB2 increased significantly(P＜0.05), on the contrary, compared with the normal group, the hepatic tissue 6-Keto-prostagland decreased significantly in the model group(P＜0.05), the treatment group also increased but P＞0.05. There was no positive expression of COX-2 in hepatic tissue of normal rats. In the model group, there was positive expression of COX-2 antigen and the number of COX positive cells progressively increased at 4, 8, 12 wks. The intensity of expression of COX-2 had significantly increased(P＜0.05) and the intensity of COX-2 expression in the treated group decreased remarkably compared with the model group(P ＜ 0.05). The expression of COX-2 mRNA and the level of COX-2 protein were significantly stronger in the liver of model rats compared with normal rats, and significantly weaker in treated rats, than in 8W and 12W model rats(P＜0.05). Conclusion:The increase of COX-2 expression in NAFLD is closely associated with the severity of liver inflammation and damage. COX-2 may play an important role in the progression of rat NAFLD, and the expression of COX-2 mRNA is downregulated by cyclooxygenase-2 inhibitor, which can depress the oxidative stress and control inflammatory response efficiently.