HHcy对ApoE^(-/-)鼠动脉粥样硬化的影响及叶酸、VB_(12)的干预效应

Effects of HHcy on atherosclerotic plaque of ApoE^(-/-)mice and interventions of Folic Acid and VB_(12)

目的探讨高同型半胱氨酸血症(HHcy)对ApoE-/-鼠动脉粥样硬化(AS)形成的影响及叶酸、维生素B1(2VB12)的干预效应。方法健康5周龄雄鼠(SPF级C57BL/6J)作为对照组,饲以普通饮食。另选5周龄雄性纯合子ApoE-/-鼠(SPF级近交系C57BL/6J)36只,随机平均分为高脂血症组、HHcy组、干预组。喂养14周后,取血测定血清Hcy及血脂水平,取主动脉进行石蜡包埋并切片,HE染色后检测主动脉斑块面积及内中膜厚度。结果 HHcy组血清同型半胱氨酸(Hcy)水平明显高于对照组与干预组(P<0.001),与对照组比较,其血脂LDL、TG、CHOL分别升高约2.2、7.6、7.2倍,HDL下降约63%(P<0.001)。HE染色可见三组ApoE-/-鼠均有AS斑块形成,HHcy组主动脉斑块面积6.21×105μm2明显大于高脂血症组3.99×105μm2与干预组4.41×105μm(2P<0.05)。AS斑块面积与其血清Hcy水平呈正相关(r=0.4898,P<0.001)。结论 HHcy导致ApoE-/-鼠AS病变形成,且病变程度依赖血清Hcy水平,叶酸和VB12的干预可有效缓解HHcy引起的血管损伤。

[ Objective ] To investigate the effects of hyperhomocysteinemia （HHcy） on atherosclerotic plaque of ApoE-/- mice and interventions of folic acid and vitamin B12 （VB12）. [Methods] Thirty six 5-week old C57BL/6J ApoE-/- mice were randomly divided into three groups, including the hyperlipidemic group, the model group and the intervention group, with 12 mice in each group. Besides, another 12 normal C57BL/6J mice were served as control group. Serum homocysteine （Hcy） and lipid changes were detected 14-week later, and the changes of plaque size, thickness of intimal and medial were measured by HE staining. [ Results ] The serum Hcy levels of the model group were significantly higher than the control group and the intervention group （P 〈0.001）. The content of LDL,TG and CHOL of the model group increased by 2.2, 7.6 and 7.2 times than that of the control group, and the content of HDL decreased 63%（P 〈0.001）. Atherosclerotic fatty plaque can be seen in the hyperlipidemic, model and intervention group. Aortic changes were attenuated in treatment group when compared to those in the model group. Serum Hcy is more closely related to atherosclerosis（AS） （r =0.4898, P 〈0.001）. [ Conclusion] HHcy can induce the formation of AS, and earlier folic acid and VB12 interference can effectively prevent the vascular injury by HHcy.