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 t...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-fat 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; real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRI33 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 significantly higher than in the control group （122.28 ± 95.37 vs 3.06 ± 2.33,P = 0.002） and group A （122.28 ± 95.37 vs 5.77 ± 4.20,P = 0.001）. There was no significant 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 significantly 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 significantly 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.展开更多
AIM： To investigate whether increased intestinal permeability contributes to the pathogenesis and progress of nonalcoholic steatohepatitis by observing its dynamic change in rat models. METHODS： Rat models of nonalc...AIM： To investigate whether increased intestinal permeability contributes to the pathogenesis and progress of nonalcoholic steatohepatitis by observing its dynamic change in rat models. METHODS： Rat models of nonalcoholic steatohepatitis were established by giving a fat-rich diet. The rats were sacrificed at wk 8, 12 and 16 during the study. Rats fed with normal diet were taken as control. Plasma D-lactate, plasma diarnine oxidase, serum lipids and liver transarninases were measured in blood of the femoral artery. Hepatic steatosis and inflammation were assessed by haematoxylin-eosin staining. RESULTS： A rat model of nonalcoholic steatohepatitis was established successfully. Plasma D-lactate level in model group at wk 8, 12 and 16 and diarnine oxidase level in model group at wk 12, 16 increased significantly compared with those in control group. There were notable differences of D-lactate and diarnine oxidase level in model group between wk 8 and 12 as well as between wk 12 and 16. Serum lipids, liver transaminases and liver injury also increased with disease development CONCLUSION： Increased intestinal permeability caused by intestinal bacterial overgrowth and endotoxin-induced intestinal destruction exists in rats with nonalcoholic steatohepatitis, which may partially explain the pathogenesis and progress of this disease.展开更多
文摘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-fat 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; real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRI33 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 significantly higher than in the control group （122.28 ± 95.37 vs 3.06 ± 2.33,P = 0.002） and group A （122.28 ± 95.37 vs 5.77 ± 4.20,P = 0.001）. There was no significant 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 significantly 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 significantly 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.
文摘AIM： To investigate whether increased intestinal permeability contributes to the pathogenesis and progress of nonalcoholic steatohepatitis by observing its dynamic change in rat models. METHODS： Rat models of nonalcoholic steatohepatitis were established by giving a fat-rich diet. The rats were sacrificed at wk 8, 12 and 16 during the study. Rats fed with normal diet were taken as control. Plasma D-lactate, plasma diarnine oxidase, serum lipids and liver transarninases were measured in blood of the femoral artery. Hepatic steatosis and inflammation were assessed by haematoxylin-eosin staining. RESULTS： A rat model of nonalcoholic steatohepatitis was established successfully. Plasma D-lactate level in model group at wk 8, 12 and 16 and diarnine oxidase level in model group at wk 12, 16 increased significantly compared with those in control group. There were notable differences of D-lactate and diarnine oxidase level in model group between wk 8 and 12 as well as between wk 12 and 16. Serum lipids, liver transaminases and liver injury also increased with disease development CONCLUSION： Increased intestinal permeability caused by intestinal bacterial overgrowth and endotoxin-induced intestinal destruction exists in rats with nonalcoholic steatohepatitis, which may partially explain the pathogenesis and progress of this disease.
