Hcy对动脉粥样硬化小鼠肝脏脂质代谢的影响  

Hcy promotes the formation of atherosclerotic and effect of liver lipid metabolism disorder in ApoE^(-/-) mice

作　　者：卢冠军[1] 杨安宁[2] 蔡欣[3] 哈丽娜[3] 杨晓玲[2] 姜怡邓[2] 

机构地区：[1]宁夏医科大学总医院,银川750004 [2]宁夏医科大学基础医学院,银川750004 [3]宁夏医科大学检验学院,银川750004

出　　处：《重庆医学》2014年第30期4030-4033,共4页Chongqing medicine

基　　金：国家自然科学基金项目资助(81160044);2012年国家自然科学基金项目资助(81260063)

摘　　要：目的探讨同型半胱氨酸(Hcy)促进ApoE基因敲除(ApoE-/-)鼠动脉粥样硬化(AS)形成同时是否对肝脏脂质代谢产生影响。方法取健康5周龄雄鼠(SPF级C57BL/6J)12只作为正常对照组,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,分为模型对照组、高同型半胱氨酸血症(HHcy)组、叶酸和VB12干预的干预组,每组12只,饲养18周后,生化分析仪测定血清Hcy及血脂总胆固醇(CHOL)、三酰甘油(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)水平,主动脉冰冻切片苏木素-伊红(HE)染色后观察并测量斑块面积;肝脏组织冰冻切片油红O染色观察肝脏细胞脂质变化,酶法测定肝脏脂质代谢改变。结果与正常对照组比较,HHcy组血清Hcy、LDL、TG、CHOL水平明显增高(P<0.01),分别升高约2.3、2.8、5.0、10.7倍,HDL下降约64%(P<0.01);干预组Hcy、LDL、CHOL水平较HHcy组分别下降43%、34%、21%,HDL水平增高36%(P<0.05),TG无明显变化;HE染色可见3组ApoE-/-鼠主动脉均有AS形成,其中HHcy组主动脉斑块面积28.2×104μm2,明显大于模型对照组的17.0×104μm2(P<0.05),干预组斑块面积17.1×104μm2,较HHcy组减轻(P<0.05)。肝脏油红O染色HHcy组脂质积累明显;干预组肝细胞内有少量脂质沉积;氧化酶法检测发现HHcy组肝脏组织中CHOL和TG分别是正常对照组的2.2、2.8倍(P<0.01);干预组肝脏CHOL、TG水平与HHcy组比较下降30%、33%(P<0.01)。结论 Hcy促进ApoE-/-鼠AS形成的同时加速肝脏脂代谢紊乱。Objective To study the effect of homocysteine（Hcy）on the formation of atherosclerotic and acceleration of ApoE-/-mice liver lipid metabolism disorder .Methods 12 normal 5 weeks old C57BL/6J mice served as control group ,and 36 5 weeks old C57BL/6J A poE-/- mice were randomly divided into 3 groups（n=12 for each group） ,the model control group ,the hyperhomocys-teinemia（HHcy）group and the intervention group（intervened by folate and vitamin B12 ） .18 weeks later ,the blood of the mice was gotten using a Unilateral enucleation method ,and the Serum Hcy and lipid changes were detected by Biochemical analyzer .And the changes of plaque size were measured by HE staining .The liver tissues of the 4 groups mice were taken and the changes in hepato-cyte lipid were detected by oil red O staining ,and the hepatic lipid levels were measured by enzymatic determination（by Semi-quan-titative image analysis） .Results The results showed that ,when compared with the control group ,the serum Hcy ,LDL ,TG and CHOL levels of the HHcy group significantly increased by 2 .3 ,2 .8 ,5 .0 ,10.7 fold（P〈0.01）and the content of HDL decreased by 64% （P〈0.01） ,and the result showed that ,conpared with the HHcy group ,the seram Hcy ,LDL and CHOL levels of the interven-tion group were significantly decreased by 43% ,34% ,21% （P〈0.05） .Atherosclerotic fatty plaque could be seen in the hyperlipi-demic ,model and intervention group .Meanwhile ,there was a large number of scattered fat in A poE-/-mice liver by oil red O staining in the HHcy group ,and the CHOL and TG levels were 2 .2 fold and 2 .8 fold higher in the HHcy than that in the normal control group respectively（P〈0.01） .And compared with the HHcy group ,the serum CHOL and TG levels of the intervention group sig-nificantly decreased by 34% ,33% （P〈0.01） .Conclusion It is found that Hcy can induce the formation of As and accelerate liver lipid metabolism disorder .

关 键 词：同型半胱氨酸 脂类代谢 动脉粥样硬化 ApoE-/-鼠 

分 类 号：R543.5[医药卫生—心血管疾病]