摘要
目的探讨同型半胱氨酸(Hcy)在apoE-/-小鼠体内对胱硫醚-β-合成酶(CBS)和亚甲基四氢叶酸还原酶(MTHFR)的影响,以及阿托伐他汀和(或)叶酸/维生素B12对肝脏CBS和MTHFR代谢系统有无改善效应。方法将80只6周龄雄性apoE-/-小鼠随机分为两组,高蛋氨酸组(n=65):2%(wt/vol)L-蛋氨酸灌胃;对照组(n=15):每天喂予等量生理盐水。喂养2月后,高蛋氨酸组死亡5只,剩余60只小鼠再平均分为四组:未治疗组(Ⅰ组)、单用阿托伐他汀组(3mg/kg)(Ⅱ组)、阿托伐他汀(3mg/kg)+叶酸(2mg/kg)+维生素B12组(30μg/kg)(Ⅲ组)、叶酸(2mg/kg)+维生素B12(30μg/kg)组(Ⅳ组)。1月后提取肝脏总蛋白,Westernblotting法检测各组肝脏组织CBS和MTHFR的相对表达量。结果Ⅰ组小鼠肝脏CBS和MTHFR的相对表达量较对照组明显下降(P<0.01),Ⅱ、Ⅲ、Ⅳ组CBS的相对表达量较Ⅰ组明显上升(P<0.05),Ⅳ组CBS和MTHFR的相对表达量基本恢复至对照组水平(P>0.05)。经药物治疗后,Ⅱ组的MTHFR的相对表达量与Ⅰ组比较差异无统计学意义(P>0.05),而Ⅲ组和Ⅳ组MTHFR的相对表达量较Ⅰ组上升(P<0.01)。结论首次证实阿托伐他汀和叶酸/维生素B12对小鼠肝脏CBS均有改善效应。叶酸/维生素B12对MTHFR有明显的改善作用,而阿托伐他汀效果不明显。
Objective To explore the influence of homocysteine （Hcy） on liver cystathionine-β-synthase （CBS） and methylenetetrahydrofolate reductase （MTHFR） system in apoE^-/- mice, and determine the effects of atorvastatin and/or folate/vitamin B12 on liver CBS and MTHFR system. Methods Eighty male 6-week-old apoE^-/- mice were randomly divided into two groups： 65 mice were fed with a chow diet containing 2% （wt/vol） L-methionine （homomethionine group） and 15 mice were fed with normal saline （control group）. Two months later, the 60 mice survived in homomethionine group were subdivided into four groups ： group Ⅰ （untreated） , Ⅱ（3 mg/kg atorvastatin） , Ⅲ （3 mg/kg atorvastatin ＋ 2 mg/kg folate ＋30 μg/kg vitamin B12 ） and Ⅳ （2 mg/kg folate ＋ 30 μg/kg vitamin B12 ）. After one month, Western blotting was performed to detect the liver CBS and MTHFR system protein expression in each group. Results The relative expression of liver CBS and MTHFR was significantly lower in group Ⅰ than in control group （ P 〈 0.01 ） , while that of liver CBS in group Ⅱ , Ⅲ and Ⅳ was significantly higer than in group Ⅰ （P 〈 0.05） , and that of liver CBS and MTHFR in group Ⅳ almost recovered to normal level. After drug treatment, there was no significant difference in the relative expression of MTHFR between group Ⅰ and group Ⅱ ,while that in group Ⅲ and Ⅳ was significantly higher than in group Ⅰ （P 〈 0.01）. Conclusion It was demonstrated for the first time that atorvastatin and folate/vitamin B12 therapy had favourable effects on liver CBS in mice. Folate and vitamin B12 can improve liver MTHFR, while atorvastatin can not.
出处
《上海交通大学学报（医学版）》
CAS
CSCD
北大核心
2009年第1期14-16,共3页
Journal of Shanghai Jiao tong University:Medical Science
基金
上海市科委重大基础研究项目资助(054119634)~~
