The Effects Of Exenatide On Artery Lesions In Model Of Atherosclerosis In Apolipoprotein E-deficient Mice

ObjectiveTo study the effects of glucagon-like peptide-1receptor agonist exenatideon glucose metabolism and lipid metabolism and aortic lesions in model ofatherosclerosis in ApoE-/-mice.Preliminary study the part of the role ofanti-atherosclerosis mechanism.Methods1. ApoE-/-mice were bred under SPF environment. ApoE-/-mice wererandomized into the normal diet group (n=14) and high-fat diet group (n=68), fedfor12weeks random testing HE staining of the aortic arch，detecting the modelunder a microscope.2. The mice of the normal diet group (n=10) and high-fat diet groups (6×each group=10) were administrated in different ways (including non drugs,atorvastatin and/or exenatide) intervention for6weeks.3. The general condition of mice was observed (such as body weight, bloodglucose). IPGTT test for the detection of glucose metabolism in mice.4. Fasting serum insulin levels in each group was measured by ELISAassay.5. Fasting lipids (TC, TG, LDL-C) levels of mice in each group weredetected by enzymatic and selective precipitation assay. 6. HE stained and then observed the change of structures of the aorticarches.7. The expression of protein of vascular cell adhesion molecule-1(VCAM-1)and intercellular adhesion molecule-1(ICAM-1) of the aorta in each group wasstudied by Western blot.Results1. Fed with high-fat diet for12weeks，under the microscope, the high-fatdiet group showed early plaque formation of AS, but hasn’t formed the lipid core,the thickening intima-media thickness compared with the normal diet group. It issuggest that AS model successful.2. After the intervention, the weight of the non-drug intervention group andthe atorvastatin group significantly increased. Atorvastatin+exenatide low-dosegroup significantly reduced blood glucose.IPGTT test results showed that eachgroup can reduce glucose tolerance in30-90min appropriately.3ELISA assay results showed that fasting serum insulin levels of theExenatide high-dose group and the atorvastatin+exenatide low/high-dosegroups were significantly decreased which comparing with the normal diet groupand non-drug intervention group (P<0.05). There was no significant differencebetween the rest of the groups (P>0.05).4. Enzymatic and selective precipitation assay results showed that fastinglipids (TC, LDL-C) levels of the non-drug intervention group and the atorvastatingroup higher than exenatide low/high-dose groups and atorvastatin+exenatidelow/high-dose groups and the normal diet group (P<0.05). The TG levels ofatorvastatin+exenatide high-dose group was higher than the normal diet group(P<0.05). The TC, LDL-C levels significantly lower than the non-drugintervention group and the atorvastatin group (P<0.05). 5. After the drug intervention for6weeks, the structures of the aortic archesby HE stain and observed showed that the normal diet group and atorvastatin+exenatide high-dose group are normal. The non-drug intervention groupformated lipid plaques,visibled lipid core.The atorvastatin group and exenatidelow/high-dose groups and atorvastatin+exenatide low-dose group showedpathological endometrium thickening widely, without lipid core.6. The results of the Western blot test, exenatide significant reduced ofVCAM-1protein expression level in the aorta, and tended to decrease ofICAM-1protein levels.ConclusionsExenatide could inhibit the formation and development of atheroscleroticlesions in ApoE-/-mice, which may partly be attributed to down-regulatingexpression of VCAM-1, ICAM-1in aorta in ApoE-/-mice, mitigating theinflammatory response of AS, also being the results of comprehensive effectssuch as reducing insulin resistance.