The Expression Of C-X-C-chemokine Receptor 7 In Atherosclerotic Apo E-deficient(ApoE^-/-) Mice And Therapeutic Impact By Atorvastatin

Objective:Atherosclerosis is one of the most common disorder among the elderly. The aim of the study is to evaluate the expression level of CXCR7(a C-X-C chemokine receptor) in atherosclerotic apoE-deficient(ApoE-/-) mice induced by high fat diet and the effects of atorvastatin on it.Methods:1. Total thirty-six 8-week-old ApoE-/-male mice were used. They were randomly divided into three groups following one week normal rodent diet: the ND control group(normal rodent diet, n=12),the HFD model group(high fat diet: 21% fat, 0.15%cholesterol,n=12) and the statins intervention group(high fat diet+atorvastatin10mg·kg-1·d-1, n=12). Atorvastatin was administered to mice after 4 weeks of high fat diet feeding.while the ND control group and the HFD control group were treated with saline. All these mice were fed for 12 weeks to establish atherosclerosis models.2. Plasma lipoprotein: Total cholesterol(TC),triglycerides(TG),LDL-C and HDL-C in the plasma of ApoE-/- mice were measured by the test kit.3. HE staining of ApoE-/-mice aortas and Oil Red O staining of the wall from ApoE-/- mice aortas were used to measure the atherosclerotic lesion burdens.4. The expression of CXCR7,p38-MAPK protein in aortas in ApoE-/- mice were examined by western blot and immunohistochemistry and the expression of Akt,eNOS protein were examined by western blot.Results:1.The animal model of atherosclerosis:After 12 weeks of high fat diet feeding, the results of the HE staining showed that lots of lesions were found in the aortas in HFD model group;the mean atherosclerotic lesion volume in HFD model group mice increased significantly accompanied by hyperlipidemia,and the En face Oil Red O staining showed the same result.2. The expression of CXCR7 on atherosclerotic lesion and the intervention byatorvastatin:2.1 The lipids detection: the blood lipid concentration of ApoE-/- mice before treated with high fat diet dealt with statistics has showed no significant difference.After 12 weeks of high fat diet feeding,Significant increases in TC,TG, LDL-C and a decrease in HDL-C were observed in mice with the high fat diet; However,there was no significant change in lipids in the statins intervention group compared with the ND control group.2.2 Pathological changes in ApoE-/- mice aortasHE staining of aortic arch and aortic valve showed that few lesions were found in the aortas in ND control group.Apparent atherosclerotic plaque burdens could be seen in HFD model group and statins intervention group, while the atherosclerotic plaque burdens in statins intervention group were notably reduced than HFD model group. And the En face Oil Red O staining detect atherosclerotic lesions showed the same trend.2.3 The expression of CXCR7Used western blot and immunohistochemistry to examine the expression of CXCR7 protein in aorta in ApoE-/- mice showed that the HFD model group and the statins intervention group were significantly decreased compared with those expression in the ND control group(P<0.01),while statins intervention group of CXCR7 protein expression were significantly increased compared with those expressions in HFD model group(P<0.01).2.4 The expression of Akt and eNOSThe expression of Akt and eNOS protein in aorta in ApoE-/- mice showed that the HFD model group and the statins intervention group were significantly decreased compared with those expression in the ND control group(P<0.01),while statins intervention group were significantly increased compared with those expressions in HFD model group(P<0.01).2.5 The expression of p38-MAPKUsed western blot and immunohistochemistry to examine the expression of p38-MAPK protein in aorta in ApoE-/- mice showed that the expression level of p38-MAPK protein was higher in HFD model group as well as the statinsintervention group than ND control group(P<0.01), and atorvastatin intervention downregulated its expression compared with HFD model group(P<0.01).Conclusion:1. High fat diet feeding induced hyperlipidemia and atherosclerosis in ApoE-/-mice.2.The atorvastatin intervention prevents or reverses hypercholesterolemiainduced atherosclerosis by inhibiting plasma cholesterol, increasing the expression of CXCR7, Akt, eNOS protein and decreasing the expression of p38-MAPK protein in the aorta,thereby decreased atherosclerosis.