Clinical Evaluation And Mechanism Of Liraglutide On Arteriosclerosis Rat Model

Objective(1)To evaluate the curative effect of liraglutide in the treatment of atherosclerosis rat model by pathology,vascular tension test and serological markers;(2)To investigate the influence of liraglutide on serum and vascular tissue PDGF-B in atherosclerosis rats and its possible mechanism.Methods(1)Thirty-two clean male Sprague-Dawley rats were randomly divided into high-fat groups and control group,and 20 rats were fed with high-fat diet,12 rats were fed with ordinary feeds.The high-fat group were randomly divided into placebo groups and liraglutide group after successful modeling,and continued to be fed with high-fat diet.liraglutide was injected subcutaneously in the liraglutide group,and the placebo group was subcutaneously injected with equal doses of saline.;(2)At the end of 16 th week of intervention,the changes of vascular wall were observed by pathological HE staining and Masson staining,the changes of vascular tone were detected by vascular tone tester,the changes of vascular function were evaluated by serological test;(3)The concentration of PDGF-B in the serum of each group was measured by Elisa,and the content of PDGF-B in the lysate of the vascular tissue was measured by Western blot;(4)Relative quantitative analysis of p-ERK1/2 and ERK1/2 protein expression in vascular cells by Western blot;(5)Record the changes of vascular tension with Chaet5 and screenshot.Image J software analyzes the gray value of protein bands.Sigma plot13.0 was used for mapping;normal distribution test was performed by using SPSS19.0 statistical software;using "x ± s" to represent all the metrological data that meet the normal distribution.One-way analysis of variance(ANOVA)was used to analyze the differences among groups,among which SNK was used for comparison.Results(1)Compared with the placebo group,the body weight,triglyceride,total cholesterol,low density lipoprotein,and serum fasting insulin in the liraglutide group were significantly decreased(P<0.05).There was no significant difference between the three groups in fasting blood glucose.The content of nitric oxide(NO)in the liraglutide group was significantly higher than that in the placebo group,and the content of endothelin-1(ET-1)was significantly lower than that in the placebo group(P<0.05).(2)Compared with the placebo group,the liraglutide group rats vascular pathology and vasodilation function test results suggest that vascular smooth muscle cell proliferation and migration was significantly reduced,reduced fibrosis;endothelial function improved;(3)The serum concentrations of PDGF-B in the placebo group were significantly higher than that of the liraglutide group and the control group,there were statistical differences(6100.00±909.10 vs 4180.44±346.31 vs 3589.28±431.72,P<0.05),but there was no statistical difference between the liraglutide group and the control group(4180.44±346.31 vs 3589.28±431.72,P>0.05).In the vascular tissue lysate,the serum concentrations of PDGF-B was significantly higher in the placebo group than that in the liraglutide group and the control group,there were statistical differences between them(0.45±0.80 vs 0.27±0.73 vs 0.22±0.65,P<0.05),and there was no significant difference between the liraglutide group and the control group in the PDGF-B content(0.27±0.73 vs 0.22±0.65,P>0.05);(4)The expression of p-ERK1/2 in the liraglutide group compared with the placebo was significantly lower,the difference was statistically significant(0.41±0.96 vs 0.29±0.83,P<0.05;0.31±0.11 vs 0.22±0.11,P<0.05),but there was no significant difference between the liraglutide group and the control group(0.29±0.83 vs 0.25±0.10,P>0.05;0.22±0.11 vs 0.15±0.05,P>0.05).There was no significant difference in the expression of ERK1/2 in each group(0.44±0.06 vs 0.44±0.05 vs 0.45±0.05,P>0.05;0.31±0.05 vs 0.30±0.02 vs 0.29±0.02,P>0.05).Conclusions(1)Liraglutide can significantly reduces body weight in rats with arteriosclerosis induced by high-fat diet,improves lipid profile and insulin resistance,protects vascular endothelial cells,and inhibits proliferation and migration of vascular smooth muscle cells;(2)Liraglutide can down-regulate the expression of PDGF-B and inhibits the proliferation and migration of vascular smooth muscle cells,thereby reducing the degree of atherosclerosis,which may be related to the inhibition of the phosphorylation of ERK1/2 by liraglutide.