Role of SDF-1/CXCR 4 in the process of quercetin against atherosclerosis in ApoE-/- mice

Abstract:

Objective：To explore quercetin on ApoE -/-mice atherosclerosis formation and expression of stromal derived factor-1（SDF-1）/CXCR4，and to provide experimental basis for anti-atherosclerosis of the quercetin. Methods：Forty 6-week-old ApoE-/-mice were divided randomly into four groups：normal control，model group and experimental group（with low-dose，mid-dose and high-dose quercetin） and were randomly are sacrificed at the time of the 10 th week and 20 th week after the administration of the drugs respectively. SDF-1 and CXCR 4 protein and gene expressions were measured by ELISA，immunohistochemical technique and real-time PCR. Results：（1）HE staining demonstrated no plaque formation in normal group and lighter plaque formation in model group than in high-fat diet group. （2）According to immunohistochemical results at the same time points：in normal group，SDF-1 was mainly existed in endothelial cells and smooth muscle cells and CXCR4 mainly existed in endothelial cells；the expression was few and the staining was light；in model group，there were abundant expression of SDF-1 and CXCR4 in smooth muscle cells and foam cells，appearing in deep brown-yellow color；in experiment group，expressions of SDF-1 and CXCR4 were decreased in all three subgroups than in model group（P=0.010）. Statistical dif－ferences were found between low-dose and mid-dose groups and normal group（P=0.000）. According to immunohistochemi－cal results at the different time points，expression of SDF-1 in model group increased in time-dependent manner（P=0.000）. （3）ELISA results of SDF-1 and CXCR4 level in serum and real-time PCR results of SDF-1 and CXCR4 mRNA expression at the same time points：expression of SDF-1 and CXCR4 was the highest in model group（compared with other groups，P=0.000） and was the lowest in normal group. The expression of SDF-1 and CXCR4 progressively decreased with the increase of the dose of quercetin，especially there was no statistical difference in CXCR4 between high-dose group normal group（P >0.05）. At different time points，SDF-1 and CXCR4 in model group increased in time-dependent manner（P=0.00）. But no apparent time dependence occurred in experiment group and normal group. Conclusion：SDF-1/CXCR 4 may promote vascular smooth muscle cell proliferation and migration to the intima，so as to thicken the intima，form foam cell and lead to plaque formation. Quercetin may inhibit the expression of SDF-1 and CXCR4 and ApoE -/- mice atherosclerosis formation，which may be one of the mechanisms of its anti- atherosclerosis.