Evaluation Of The Therapeutic Effect And Study On Its Mechanism Of Liraglutide On Rats With Nonalcoholic Fatty Liver Disease

Objective(1)By using proton magnetic resonance spectroscopy,pathology and serum index to evaluate the clinical efficacy of liraglutide in the treatment of nonalcoholic fatty liver in rats;(2)To investigate the effect and its possible mechanism.of liraglutide on Fibroblast growth factor 21 levels in serum and hepatic tissue in rats with nonalcoholic fatty liver disease.Methods(1)Thirty two clean male SD rats were selected,and randomly divided into high fat diet(HFD)group and control(CON)group.HFD group were fed with high fat diet,then randomly divided the HFD group into liraglutide group(HFD+Lira group)and placebo group(HFD+PL group)after model were successfully made,and all the rats still were fed with high fat diet and respectively injected with liraglutide or saline everyday,CON group were fed with normal food;(2)After 16 weeks of treatment,the hepatic triglyceride content of each rat was detected by ~1H-MRS,liver tissue was detected by HE stain,serum index and liver homogenate were tested;(3)Enzyme linked immunosorbent assay was used to measure the concentration of serum Fibroblast growth factor 21 in three groups;Western blot was used to determine the content of Fibroblast growth factor 21 in liver tissue lysate;(4)Comparative study on the expression of Peroxisome Proliferator-activated receptor ? and Peroxisome Proliferator-activated receptor ? protein in liver cells by immunohistochemistry;(5)Image J software was used to analyze the gray value of protein bands;IPP software was used to analyze the immunohistochemical protein content;Using SPSS 17 statistical software for test of normal distribution,using Sigma plot 12.5 mapping,with normal distribution measurement data was expressed as “?x±s”;The differences between groups were analyzed by single factor analysis of variance,among groups were compared with SNK test;Ordered qualitative data using multiple independent sample rank sum test?Results(1)Compared with the HFD+PL group,the body weight,liver index,homeostasis model of assessment for insulin resistance index and fasting insulin,triglyceride,cholesterol,low densith lipoprotein,alanine aminotransferase in the serum of rats and triglyceride and cholesterol of liver homogenate were significantly decreased in the HFD+lira group,the difference was statistically significance(P<0.05);There were no significant difference in level of fasting blood suger and high density lipoprotein in three groups;(2)Compared with HFD+PL group,the result of~1H-MRS and liver tissue in pathological in HFD+Lira group showed that liver steatosis was significantly improved,some of them even become normal,the content of fat in liver is decreased(26.8±1.30 vs 13.0±0.71,P<0.05);(3)The serum levels of fibroblast growth factor 21 in the placebo group were significantly higher than those in the liraglutide group and the control group(637.53±14.12 vs 509.49±18.84,P<0.05),and there was no significant difference between the liraglutide group and the control group(509.49±18.84 vs 503.98±20.23,P>0.05);Liver cell lysate,the content of Fibroblast growth factor 21 in the placebo group was obviously lower than that of liraglutide group and control group(1.38±0.23 vs 2.50±0.78 vs 2.46±0.49,P<0.05);Liraglutide group and the control group FGF21 showed no significant difference(2.50±0.78 vs 2.46±0.49,P>0.05);(4)The expression of peroxisome proliferator-activated receptor ? in the placebo group was significantly lower than that in the liraglutide group and the placebo group(0.50±0.07 vs 0.67±0.06,P<0.05).There was no significant difference between the liraglutide group and the control group(0.67±0.06 vs 0.71±0.07,P>0.05);(5)Compared with the control group,the expression of peroxisome proliferator-activated receptor ? in the liraglutide group and placebo group was decreased(0.73±0.06 vs 0.65±0.56 vs 0.62±0.06,P<0.05),and its expression in the liraglutide group was higher than in the placebo group,but the difference was no statistically significance(0.65±0.56 vs 0.62±0.06,P>0.05).Conclusions(1)Liraglutide can significantly improve the body weight,liver index and decrease the content of liver fat in the rats with nonalcoholic fatty liver disease induced by high fat diet,thus,it possibly can be a promissing drug in the treatment of nonalcoholic fatty liver disease;(2)Liraglutide improves nonalcoholic fatty liver disease,promote the expression of fibroblast growth factor 21,its mechanism may be related to the up regulation of Peroxisome Proliferator-activated receptor ? expression of liraglutide.