Abstract: Objective: To investigate the therapeutic effect of folic acid combined with vitamin B12 on atherosclerosis induced by hyperhomocysteinemia in the rats, and to elucidate its therapeutic mechanism. Methods: Thirty-three rats were randomly divided into control group, model group and treatment group (n=11).The rats in control group were given normal diet,the rats in model group were given normal diet and methionine,and the rats in treatment group were given normal diet, methionine, perfused folic acid and vitamin B12. The histopathological changes of thoracic aorta of the rats were observed by HE staining. The levels of serum Hcy and matrix metalloproteinase-9 (MMP-9) were detected with ELISA,and the expression levels of CCR5 and CC chemokine ligand 5 (CCL5) proteins in thoracic aortic smooth muscle cells were detected by immunohistochemical staining. The expression levels of CCR5 and CCL5 mRNA in thoracic aortic smooth muscle cells were detected by RT-PCR. Results: The results of HE staining showed that the medial smooth muscle cells of the rat thoracic aorta were arranged neatly in control group, the intimal elastic membrane was complete and the endothelial cells were continuous; the smooth muscle cells of the thoracic aorta were loose in model group, the endometrium was damaged, the foam cells were formed under the intima, and the endothelial cells were necrotic;the pathological changes of the thoracic aorta of the rats in treatment group were between control group and model group. The levels of serum Hcy of the rats in model group and treatment group were higher than that in control group (P<0.05); the serum Hcy level in treatment group was lower than that in model group (P<0.05).The levels of serum MMP-9 of the rats in model group and treatment group were higher than that in control group (P<0.05);the serum MMP-9 level in treatment group was lower than that in model group (P<0.05).The expression gray values of CCR5 and CCL5 proteins in the thoracic aortic smooth muscle cells of the rats in rats in model group and treatment group were lower than those in control group (P<0.05); the expression gray values of CCR5 and CCL5 proteins in the thoracic aortic smooth muscle cells of the rats in treatment group were higher than those in model group (P<0.05).The relative expression levels of CCR5 and CCL5 mRNA in the thoracic aortic smooth muscle cells of the rats in model group and treatment group were higher than those in control group (P<0.05);the relative expression levels of CCR5 and CCL5 mRNA in the thoracic aortic smooth muscle cells of the rats in treatment group was lower than that in model group (P<0.05). Conclusion: Folic acid combined with vitamin B12 could decrease the serum Hcy and MMP-9 levels and the expression levels of CCR5 and CCL5 in the thoracic aortic smooth muscle cells which may be one of the mechanisms of folic acid combined with vitamin B12 in the treatment of atherosclerosis.

Key words: atherosclerosis, folic acid, vitamin B12, matrix metalloproteinase-9, CC-type chemokine receptor 5, CC-type chemotactic cytokine 5