Effects Of Liraglutide On ERp46 Protein And Adiponectin And Oxidative Stress In Rats With Non-alcoholic Fatty Liver Disease

Objective To investigate the effects of liraglutide on ERp46 protein and adiponectin and oxidative in rats with non-alcoholic fatty liver disease(NAFLD),and to further explore the possible mechanism of liraglutide in improving fatty liver.Methods(1)Molding: Thirty two clean-grade male SD rats were randomly divided into 2 groups:high fat group(n=20)and normal control group(n=12).The high fat group was given high fat diet for 12 weeks.Two rats were randomly killed at the end of 12 weekends.The liver tissue of the same part was taken for pathological results to confirm the model of nonalcoholic fatty liver disease successfully established.(2)Intervention: After NAFLD model were successfully established,the non-alcoholic fatty liver disease rats were randomly divided into the placebo group(n=9)and the liraglutide group(n=9),and the high-fat diet was continued to be given,and the rats were given a subcutaneous injection of the liraglutide[0.6 mg/(kg·d)] and the equivalent volume of normal saline respectively,and the total intervention was 16 weeks.(3)Detection: Rats were all killed at the end of 28 weeks,the levels of weight,liver mass,biochemical index and inflammatory factors were measured,and observed hepatic histopathological hematoxylin-eosin staining.Real-time PCR and western blot were used to detect the expression of Endoplasmic Reticulum protein 46(ERp46)m RNA and protein in liver tissue.(4)Statistics: The statistical software of SPSS 21.0 was used for analysis,and Sigma plot12.5 was used to drawing,with normal distribution measurement data was expressed as “(?)±s”.The single-factor analysis of variance was used for the comparison among the groups.The two comparisons between the groups were tested by the SNK method.The image J software analyzed the gray value of the western blot protein band,and the correlation between the expression level of the ERp46,the adiponectin and the oxidative stress index was analyzed by the pearson correlation analysis.Results(1)Compared with placebo group,the body weight,homeostasis assessment-insulin resistance,liver index,serum alanine aminotransferase,fasting insulin,triglyceride,cholesterol,low density lipoprotein level were decreased and serum adiponectin level increased in liraglutide group,the results were statistically different.(2)Compared with placebo group,the levels of triglyceride,cholesterol,free fatty acid,tumor necrosis factor α,malondialdehyde(MDA)in liver homogenate were decreased,the levels of superoxide dismutase(SOD)and adiponectin in liver homogenate were increased,and the degree of steatosis in liver decreased in liraglutide group,the results were statistically different.(3)Compared with the placebo group,the expression of ERp46 mRNA and protein in the liver tissue of the liraglutide group was increased,and the difference was of statistical significance.(4)There was no significant difference in the indexes between liraglutide group and control group.Conclusion The mechanism of liraglutide in improving non-alcoholic fatty liver may be related to the up-regulation of ERp46 protein expression and adiponectin level in liver tissue,and inhibition of endoplasmic reticulum stress and alleviation of oxidative stress in liver tissue.