Abstract: Objective   To evaluate the effect of probucol, folic acid and vitamin B12 combined medication on vascular endothelial dysfunction induced by hyperhomocysteinemia in rats. Methods   Seventy male SD rats were randomly divided into seven groups. Each group had ten rats: normal control group, Hhcy group, low-dose- probucol group, middle-dose- probucol group, high-dose- probucol group, folic-acid-vitamin B12 group, folic-acid-vitamin B12 and probucol group(combination treatment group). The normal control group was fed on plain feedstuff for twelve weeks. Other groups were fed on homomethionin feedstuff for twelve weeks .And then from the eighth week added six kinds of intervention measures for four weeks，such as water, probucol(three kinds of dose), folic acid and vitamin B12,folic acid and vitamin B12 and probucol. The plasma concentrations of the homocysteine(Hcy) , oxidation low density lipoprotein(OX-LDL)，nitric oxide（NO）levels were measured at the beginning ,the eighth week and the twelveth week. Hcy were measured by high pressure liquid chromatography analysis (HPLC). OX-LDL and NO were measured by enzyme-linked immunoassay (ELISA) method. Results   After adding high concentrations of methionine feedstuff, the level of Hcy was significantly higher than that normal control group (P<0.05) while the level of OX-LDL increased and the level of NO decreased. After four week intervention, the levels of Hcy, OX-LDL and NO in groups added the three different doses probucol, and added the folic acid and vitamin B12 had statistically differences compared with normal control group(P<0.05). The plasma levels of Hcy and OX-LDL in the combination treatment were lower than other intervention groups(P<0.05) while the level of NO was more obviously higher(p<0.05). The Hcy, OX-LDL and NO levels in the combination treatment group had not statistically significant (P > 0.05) compared with normal control group. The levels of Hcy, OX-LDL and NO had no statistically differences (P >0.05) in groups added the three different doses probucol of rats . Correlation analysis showed Hcy levels were positively correlated with OX-LDL levels(P<0.05). Conclusion   The present study demonstrated that OX-LDL interacted with Hcy, leading to endothelial dysfunction possiblely . With probucol,folic acid and vitamin B12 combined medication, the level of Hcy and OX-LDL could be decreased more significantly, meanwhile the level of NO increased , and thus the endothelial function was improved, which may slow down the development of atherosclerosis.

Key words: homocysteine, folate, Vitamin B12, lipoproteins, LDL, nitric oxide, disease models, 动物