Abstract
Objective: To investigate the protective effect of celecoxib against non-alcoholicsteatohepatitis and its impact on the expression of peroxisome proliferator-activated receptor gamma (PPARγ)/NF-κB in type 2 diabetes rats. Methods: Thirty-six male Sprague-Dawley rats were randomly and equally divided into three groups: control group, model group, and model+celecoxib group. After the model was successfully established, all rats were sacrificed to isolate serum and liver tissues. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, liver pathological changes were analyzed by HE and oil red O staining, and the protein expression of hepatic PPARγ, NF-κB p65, and COX-2 was determined by immunohistochemistry and Western blot. Results were statistically analyzed by t-test. Results: The levels of ALT and AST in the model group (301.8±5.40 and 345.4±9.63 U/L) were significantly higher than those in the control group (33±4.06 and 76.6±7.64 U/L) and those in the model+celecoxib group (88.8±13.07 and 99.8±20.51 U/L). HE and oil red O staining demonstrated hepatic steatosis and inflammation in liver tissues. Immunohistochemical results showed that the integral optical densities (IODs) of NF-κB p65 and COX-2 in the model group (4.04E5±2.42E4 and 6.62E5±2.64E4) were significantly higher than those in the control group (4.23E4±6.82E3 and 4.82E4±3.71E3) (t= 48.86 and 72.93, bothP< 0.01) and those in the model+celecoxib group (2.74E5±4.38E4 and 2.31E5±2.09E4) (t= 9.02 and 40.51, bothP< 0.01). There was no significant difference in the IOD of PPARγbetween the model group (4.50E4±2.38E3) and the control group (4.26E4±5.09E3). However, the IOD of PPARγin the model+celecoxib group (3.22E5±1.54E4) was significantly higher than that in the model group (t= 61.82,P< 0.01). Western blot analysis showed that the relative protein levels of hepatic NF-κB p65 and COX-2 in the model group (4.93±0.76 and 3.04±0.23) were significantly higher than those in the control group (1.00±0.13 and 1.00±0.15) (t= 11.44 and 16.64, bothP< 0.01) and those in the model+celecoxib group (2.44±0.32 and 1.26±0.11) (t= 6.80 and 15.81, bothP< 0.01). The relative protein level of hepatic PPARγin the model+celecoxib group (0.98±0.09) was significantly higher than that in the model group (0.37±0.03) (t= 15.08,P< 0.01). Conclusion: Celecoxib protects type 2 diabetes rats against non-alcoholic steatohepatitis probably via modulating the expression of PPARγand NF-κB.