Experimental Study On The Expression Of COX-2and Nrf-2Associated With The Process Developed Of Nonalcoholic Fatty Liver Disease

BACKGROUND:Cyclooxygenase-2(COX-2) as the key enzyme in the metabolism of arachidonic acid is involved in the response and modulation of inflammatory. NF-E2-related factor2(Nrf-2) is one of important antioxidant proteins associated with the protective effect on cells, possibly including on the liver injury-mediated by acute and chronic inflammation. Nonalcoholic fatty liver disease(NAFLD) presents liver pathology characterized by chronic fat inflammatory. And its mediated mechanism mainly having relevance to oxidative stress(OS) and insulin resistance(IR) was considered Moreover, OS and IR closely affected the expression of COX-2and Nrf-2in liver. Therefore, the relation between COX-2, Nrf-2and the inflammatory process of NAFLD has noted.OBJECTIVE:The aim of this experimental study was to explore the correlation between the expression of COX-2, Nrf-2and the inflammatory process in liver of NAFLD model rat; And meanwhile, using transmission electron microscopy to observe the changes in liver cell morphology of NAFLD model rat with the inflammation process.METHODS:Wistar55male rats were randomly divided into the control group (C), and model group (M). There was no significant difference in body weight between the two groups. All the rats were fed under Specific Pathogen Free (SPF) condition for12weeks. Based on ordinary diet, the rats in group M were fed by gastric perfusion with high fat diet. And the rats in group N were fed with0.95%NS instead. The rats in group M were executed at the end of the4th,8th and12th week. The rats in group C were executed at the end of the12th week. The rats in body mass, liver size, liver index, AST and ALT serum level were measured. Ten rats in group M were induced by nonselective cyclooxygenase inhibitor Asprin from8week to12week(Asprin group). The expression of COX-2and Nrf-2were detected using immunohistochemical method in group C, group M and Asprin group separately. The correlation between COX-2, Nrf-2and the development process of NAFLD will be evaluated.RESULTS:Compared with group C, the liver of group M presented characteristic change with fatty infiltration, and the degree of lipotoxicity inflammatory increased with the experimental time with4week,8week and12week. All these pathological findings accorded with the diagnostic criteria of NAFLD. Some improvement of liver inflammation can be found in Asprin group; Compared with group C(12week), the expression of COX-2and Nrf-2was upregulated in rat liver of group M than that in group C (p<0.05) and presented the positive correlation markedly(r=0.96944,p<0.0001). Also compared with group C(12week), the expression of COX-2was downregulated in Asprin group; but there was no change for the expression of Nrf-2. The liver cell morphology changes in NAFLD model rat with the inflammation process were significant.CONCLUSION:COX-2in synergy with Nrf-2might be involved in the regulation of the inflammation process in NAFLD. The study implicated that COX-2could not only effect the development of inflammation in NAFLD but also could activate the expression of Nrf-2pathway, which could promote the effect of Nrf-2protecting the cell against oxidant stress in NAFLD. The further study is well worth making efforts to confirm the role of Cyclooxygenase inhibitor reversing the early pathological damage, liver fibrosis and even hepatocellular carcinoma occurrence in NAFLD.