论文部分内容阅读
AIM:To evaluate the possible role of Tribble 3(TRB3) in a rat model of non-alcoholic fatty liver disease(NAFLD) and its signal transduction mechanism.METHODS:Thirty Sprague-Dawley rats were randomized into three groups:normal control group,non-alcoholic fatty liver group A(fed on a high-fat diet for 8 wk) and group B(fed on a highfat diet for 16 wk) .To determine the degree of hepatic steatosis in rats of each group,livers were stained with hematoxylin and eosin,and evaluated;realtime fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRB3 mRNA;and Western blotting analysis was done to determine the expression levels of protein kinase B(Akt) and phosphorylated protein kinase B(p-Akt-Thr308,p-Akt-Ser473) .RESULTS:Hepatic steatosis was evident in both NAFLD groups:mild to moderate hepatic steatosis occurred in group A,mainly as mild steatosis.Moderate to severe hepatic steatosis occurred in group B,mainly as severe steatosis.The expression level of TRB3 mRNA in group B was signifi cantly higher than in the control group(122.28 ± 95.37 vs 3.06 ± 2.33,P = 0.001) and group A(122.28 ± 95.37 vs 5.77 ± 4.20,P = 0.001) .There was no signif icant difference in the expression levels of Akt(1.03 ± 0.53 vs 1.12 ± 0.77,P = 0.729) and p-Akt-Thr308(0.82 ± 0.45 vs 0.92 ± 0.38,P = 0.592) between group A and the control group.The expression level of Akt and p-Akt-Thr308 in group B was signifi cantly lower than in group A(Akt 0.41 ± 0.16 vs 1.12 ± 0.77,P = 0.008;p-Akt-Thr308 0.47 ± 0.19 vs 0.82 ± 0.45,P = 0.036) and the control group(Akt 0.41 ± 0.16 vs 1.03 ± 0.53,P = 0.018;p-Akt-Thr308 0.47 ± 0.19 vs 0.92 ± 0.38,P = 0.010) .The expression level of p-Akt-Ser473 in group A was signif icantly higher than in group B(1.48 ± 0.50 vs 0.81 ± 0.39,P = 0.041) as well as the control group(1.48 ± 0.50 vs 0.45 ± 0.26,P = 0.003).CONCLUSION:TRB3 blocks insulin signaling by inhibiting Akt activation,which contributes to insulin resistance.It may be an important factor in the occurrence and development of NAFLD.
AIM: To evaluate the possible role of Tribble 3 (TRB3) in a rat model of non-alcoholic fatty liver disease (NAFLD) and its signal transduction mechanism. METHODS: Thirty Sprague-Dawley rats were randomized into three groups: normal control group, non-alcoholic fatty liver group A (fed on a high-fat diet for 8 wk) and group B (fed on a high diet diet for 16 wk). To determine the degree of hepatic steatosis in rats of each group, livers were stained with hematoxylin and eosin, and as; realtime fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRB3 mRNA; and Western blotting analysis was done to determine the expression levels of protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt-Thr308, p-Akt-Ser473) .RESULTS: Hepatic steatosis was evident in both NAFLD groups: mild to moderate hepatic steatosis occurred in group A, mainly as mild steatosis. Moderate to severe hepatic steatosis occurred in group B, mainly as severe s teatosis. The expression level of TRB3 mRNA in group B was signifi cantly higher than in the control group (122.28 ± 95.37 vs 3.06 ± 2.33, P = 0.001) and group A (122.28 ± 95.37 vs 5.77 ± 4.20, P = 0.001). There was no signif icant difference in the expression levels of Akt (1.03 ± 0.53 vs. 1.12 ± 0.77, P = 0.729) and p-Akt-Thr308 (0.82 ± 0.45 vs 0.92 ± 0.38, P = 0.592) between group A and the control group. The expression level of Akt and p-Akt-Thr308 in group B was signifi cantly lower than in group A (Akt 0.41 ± 0.16 vs 1.12 ± 0.77, P = 0.008; p-Akt-Thr308 0.47 ± 0.19 vs 0.82 ± 0.45 , P = 0.036) and the control group (Akt 0.41 ± 0.16 vs 1.03 ± 0.53, P = 0.018; p-Akt-Thr 308 0.47 ± 0.19 vs. 0.92 ± 0.38, P = 0.010) .The expression level of p-Akt-Ser 473 in group A was signif icantly higher than in group B (1.48 ± 0.50 vs 0.81 ± 0.39, P = 0.041) .CONCLUSION: TRB3 blocks insulin signaling (1.48 ± 0.50 vs 0.45 ± 0.26, P = 0.003) by inhibiting Akt activation, which cont ributes to insulin resistance. It may be an important factor in the occurrence and development of NAFLD.