Effects And Mechanism Of Folic Acid And Vitamin B₁₂ On Hyperhomocysteinemia Resulting In Atherosclerosis

Objective:To observe the effects of folic acid and Vitamin B12 supplementation on hyperhomocysteinemia(HHcy) caused by homomethionin and the expression of matrix metalloproteinases-9(MMP-9), and to discuss the prevented effects and mechanism of this type of atherosclerosis.Methods:30 Wistar Rats were randomly divided into three groups:normal control group, the homomethionin feeding group, and the drug intervention group. They were fed 8 weeks respectively with normal diet, normal diet plus methionin(20g/kg), and normal diet plus methionin(20g/kg),folic acid 0.5mg and Vitamin B12 25ug. At the end of the 8th week, all the rats were Cut off food supply for 12h, and then were injected into abdominal cavity by 25% urethane (0.4mL/100g) to make them anesthetic.The arterial blood was obtained from abdominal aorta. The levels of total plasma homocysteine (Hey) and the content of MMP-9 protein in arterial blood were measured by enzyme-linked immunosorbent assay(ELISA). Meanwhile, the two sides carotid artery were also gained. One side carotid artery sample was randomly taken and was preserved in-70°refrigerator. The expression of MMP-9 mRNA in carotid artery was detected by the Polymerase Chain Reaction(PCR). The other side was used for hematoxylin-eosin staining. Then SPSS software was used to statistics ordered data by one-way anova analysis. Sigmaplot software was used to statistics plotting.Result:①The homomethionin diet could significantly induce HHcy for 8 weeks feeding(P < 0.01);②Compared with control group, the level of Hey in methionine group was significantly higher(P<0.05). Meanwhile,the expression of MMP-9 and the level of MMP-9 mRNA in methionine group was significantly higher than the control group(P< 0.05; P< 0. 01);③Compared with methionine group, the level of Hey in intervention group was significantly lower(P<0.05); and the expression of MMP-9 and the level of MMP-9mRNA was significantly lower, (P< 0.05; P< 0.01);④Correlation analysis showed the level of Hcy had positive correlation with level of MMP-9;⑤There were hyperplasia and derangement of smooth muscle, syzygium of elastic fibers on aortic tunica media in methionine group.which were not found in control group and intervention group.Conclusion:MMP-9 may play an important role in arterial injury caused by the HHcy. The drug intervention group can effectively reduce the HHcy and the HHcy-induced arterial injury.This effects are not only related to folic acid and VB12 treatment which can decline Hcy level in the plasma, but also related to reducing the expression of MMP-9.