普罗布考联合叶酸、维生素B12对高同型半胱氨酸血症大鼠内皮功能的影响

【摘要】 目的 探讨普罗布考联合叶酸及维生素B12对高同型半胱氨酸血症(HHcy)大鼠内皮功能的影响。方法 将70只雄性SD大鼠随机分为7组,每组10只:对照(A)组,HHcy模型(B)组,低、中、高剂量普罗布考(C、D、E)组,叶酸+维生素B12(F)组,叶酸+维生素B12+普罗布考(G)组。A组给予普通饲料喂养12周,自第8周末予蒸馏水灌胃4周;其他6组给予2%蛋氨酸饲料12周,自第8周末分别给予蒸馏水、不同剂量普罗布考(340、510、680mg·kg-1·d-1、叶酸+维生素B12、叶酸+维生素B12+普罗布考灌胃4周。分别于实验开始、实验第8、12周末测定大鼠血浆同型半胱氨酸(Hcy)、氧化低密度脂蛋白(OX-LDL)、NO浓度。结果 高蛋氨酸饮食8周末,与A组比较,B组大鼠血浆Hcy、OX-LDL升高,NO水平降低,差异均有统计学意义(P<0.05)。12周末,C、D、E及F组血浆Hcy、OX-LDL水平较B组降低,NO水平升高,与A组差异亦有统计学意义(P<0.05)。G组血浆Hcy、OX-LDL水平较B组下降,NO水平升高,差异有统计学意义(P<0.05),但与A组差异无统计学意义(P>0.05)。血浆Hcy与OX-LDL呈正相关(r=0.823,P<0.05)。结论 普罗布考联合叶酸及维生素B12能更显著地降低Hcy水平,对改善血管内皮功能,减缓动脉粥样硬化具有重要意义。

Study of the Intervention Treatment of Probucol,Folic Acid and Vitamin B12 Combined Medication on Hyperhomocysteinemia in Rats

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.