Effects Of Telmisartan On Hepatic Fat Content And Inflammation In NAFLD Rats

Objective:Effect of telmisartan on high glucose and high fat feeding nonalcoholic fatty liver disease(NAFLD) in rat liver fat content and inflammation,and to explore the protective mechanism of telmisartan on the liver.Methods:1.Preparation of animal model:a total of 34 healthy male SD rats of 6-8 weeks of age,were selected and randomly divided into two groups after 1 weeks of adaptive feeding:Normal control group(n=8),given normal diet 36 weeks;NAFLD model group26,treated with 36 weeks of high-fat diet feeding(70% of normal feed+20% lard+10%sucrose+1% cholesterol+0.25% cholic acid) and experimental animals with free access to food and water.In the 24 th week the NAFLD model group randomly selected 2 rats liver tissue pathological examination identified model was made successfully.2.Experimental grouping:NAFLD model group after successful modeling and divided for three sub group were observed for 12 weeks:NAFLD control group(n=8):continue to give a high-fat diet for 12 weeks;telmisartan intervention group(n=8):give high sugar high fat diet and telmisartan 5mg/(kg·d),gavage for 12 weeks intervention;physiological saline control group(n=8),giving high fat and high sugar diet and volume of physiological saline gavage for 12 weeks intervention.3.The body weight of rats,liver wet weight and the liver index changes:measured every 4 weeks and record the body weight of rats.At the end of the 36 th week,observe thegeneral condition of the rats,weight measurement.Rats were sacrificed after application of electronic balance weighing liver wet weight,and the liver index is calculated according to the following formula:liver index=(liver wet weight/body weight)×100%.4.Serum detection of chemical indexes:urethane anesthetized and blood samples were obtained via the abdominal aorta.Serum samples were obtained,the application automatic serum biochemical analyzer to detect alanine aminotransferase enzyme(ALT)and other biochemical indicators.5.Hepatic tissue pathology examination:take the right lobe of the liver tissue for pathological paraffin section,stained with hematoxylin-eosin(HE),liver tissue pathology examination and NAS integral evaluation.6.NF-κB protein expression:By western Blot determination of NF-κB protein expression level in liver tissue and quantitative analysis.Results:1. Changes of body weight,liver wet weight and liver index in rats:The weekend of36,compared with the normal control group,NAFLD model group,saline control group and telmisartan intervention group,the body weight were significantly higher(P<0.01);saline control group compared with NAFLD model group,body weight did not change significantly; telmisartan intervention group,compared with saline control group,the body weight decreased significantly(P<0.01).Compared with the normal control group,NAFLD model group,saline control group and telmisartan intervention group wet liver weight and liver index were significantly higher(P<0.05);compared with NAFLD model group,in control saline group, the liver wet weight and liver index were not significantly changed;compared with saline control group,telmisartan intervention group wet liver weight and liver index decreased,the difference was not statistically significant.2. Changes of liver function index:After 12 weeks of treatment,compared with the normal control group(38.33±6.98U/L) compared,NAFLD model group(87.83±12.06U/L)and physiological saline control group(86.50±13.41U/L) and the intervention of telmisartan group(60.50±17.80U/L) ALT were significantly higher(P<0.01);compared with NAFLD model group,saline control group ALT had no obvious change;compared with saline control group,telmisartan intervention group ALT decreased significantly(P<0.01).3. Histopathological examination of liver:After 12 weeks of treatment,compared with the normal control group,NAFLD model group and normal saline control group,rat liver tissue HE staining results were visible diffuse fatty degeneration,liver cell volume increased significantly,nucleus is located in the edge,with most of the cells were vacuolated,cytoplasm visible and macrovesicular lipid droplets deposition,ballooning become common,cytoplasm rarefaction,a large number of inflammatory cell infiltration in the hepatic lobule and portal area, spotty necrosis foci,NAS points higher(P<0.01).With the saline control group compared,telmisartan intervention group,the liver HE staining results was found in liver cells of reduced volume,volume of lipid droplets smaller In order to small,in the bubble of lipid droplets,the balloon like change and the inflammation of the inside of the leaflets were significantly improved,NAS score decreased(P<0.05).4. Comparison of expression levels of NF-κB:After 12 weeks of treatment,compared with the normal control group(18.53±2.51) compared,NAFLD group(86.67±11.57),saline control group(85.50±12.96) and the intervention of telmisartan group(61.00±10.20) NF-κB protein expression were significantly increased(P<0.01);Compared with NAFLD model group,saline control groups of the NF-κB protein expression had no obvious change;compared with saline control group,telmisartan intervention groups of the NF-κB protein expression decreased significantly(P< 0.05).Conclusion:Long term high glucose and high fat diet feeding may be causing the rat liver fat content increased significantly and inflammatory cell infiltration,the occurrence of NAFLD.telmisartan can by reducing liver weight,improve liver enzymes,reduce the fat content of the liver,reduce inflammation,reduce the expression of NF-κB protein,the liver to protect.