叶酸、维生素B_6和维生素B_(12)对高同型半胱氨酸血症大鼠心室重构的影响

Effect of Folic Acid,VitB_6 and VitB_(12) on Cardiac Remodeling of Hyperhomocysteinemia Wistar Rats

目的探讨叶酸、维生素B6和维生素B12能否通过降低高同型半胱氨酸血症(HHcy)大鼠血浆同型半胱氨酸(Hcy)水平,从而降低心肌基质金属蛋白酶9(MMP-9)表达,减少心肌纤维化,改善心室重构。方法选取雄性Wistar大鼠60只,随机分为正常组(A组,20只,喂食基础饲料)、HHcy组(B组,20只,喂食基础饲料加1.7%蛋氨酸)、药物干预组(C组,20只,喂食高蛋氨酸饲料加B族维生素)。于第8周检测各组大鼠血浆Hcy水平,以彩色多普勒超声诊断仪评价心功能,同时光镜下观察3组大鼠心肌病理组织学改变,免疫组化法测定心肌组织MMP-9的表达,Masson染色观察心肌纤维化程度。结果实验8周后:(1)A、B、C组大鼠血浆Hcy水平分别为(9.2±0.9)μmol/L、(39.2±2.1)μmol/L、(11.2±1.3)μmol/L,A组、C组大鼠血浆Hcy水平低于B组,差异有统计学意义(P<0.01)。(2)A组、C组大鼠左心室质量(LVW)/体质量(BW)和左心室舒张末期内径(LVEDd)较B组降低,而射血分数(EF)、左心室舒张末期后壁厚度(LVPWd)和左心室短轴缩短率(FS)均较B组升高,组间比较差异有统计学意义(P<0.01)。(3)B组和C组大鼠心肌MMP-9表达量及心肌胶原纤维化高于A组,而C组大鼠心肌MMP-9表达量及心肌胶原纤维化低于B组,组间比较差异有统计学意义(P<0.01)。结论叶酸、维生素B6和维生素B12联合应用可减少HHcy大鼠心肌MMP-9的表达,减轻心肌纤维化,改善心室重构。

Objective To investigate whether folic acid,vitamin B6 and vitamin B12 can decrease the expression of MMP-9 by reducing the level of Hcy of HHcy rats in order to alleviate myocardial fibrosis and improve cardiac remodeling. Methods 60 male Wistar rats were randomly divided into control group（group A,20 rats,fed with normal feeds）,HHcy group（group B,20 rats,fed with normal 1.7% methionine） and drug intervention group（group C,20 rats,fed with feeds with high methionine and folic acid,VitB6 and VitB12）.The rats were studies as follows after 8 weeks treatment：the level of Hcy was detected;cardiac function was evaluated by echocardiography;histopathology of myocardium was examined with light microscope;protein expression of matrix metalloproteinases-9（MMP-9） was detected by immunohistochemical method;collagen fiber of myocardium was quantitatively analyzed by Masson stain. Results After 8 weeks treatment：（1）The Hcy levels of the three groups were（9.2±0.9）μmol/L,（39.2±2.1）μmol/L and（11.2±1.3）μmol/L respectively,and the levels of group A and group C were significantly lower than group B（P0.01）.（2）The LVW/BW and LVEDd of group A and group C were significantly lower than group B,but EF,LVPWd and FS were significantly higher than group C（P0.01）.（3）The expression of MMP-9 and level of collagen fibrosis in group B and group C were significantly lower than group A（P0.01）,and so was group C compared with group B（P0.01）. Conclusion The supplement with folic acid,VitB6 and VitB12 may decrease the protein expression of MMP-9,alleviate myocardial fibrosis and prevent the cardiac remodeling through reducing the homocysteine level in hyperhomocysteinemia rats.