中文摘要：

目的探讨高同型半胱氨酸血症（HHcy）对载脂蛋白E基因敲除鼠（ApoE-/-鼠）心肌酶谱变化的影响及其与P53基因的相关性分析。方法分组：正常对照组（n=12）选择健康5周龄雄性c57BL／6J小鼠（SPF级），饲以正常饮食；另选用SPF级近交系c57BL／6J背景5周龄雄性ApoE-/-小鼠36只，随机分为3组，每组12只：ApoE-/-鼠对照组、高蛋氨酸组、干预组，分别给予正常饮食、正常饮食加1．7％蛋氨酸、正常饮食加1．7％蛋氨酸加0．006％叶酸及0．0004％维生素B12。喂养14周后，分离血清，用全自动生化分析仪检测血清中同型半胱氨酸和心肌酶谱含量，酶联免疫吸附法检测血清中氧化型低密度脂蛋白含量，实时定量PCR和免疫组织化学法检测心脏P53mRNA和蛋白表达。结果ApoE。一对照组、高蛋氨酸组及干预组中血清同型半胱氨酸均升高，其中以高蛋氨酸组升高最显著（P〈0．01）；氧化型低密度脂蛋白含量亦平行升高，与对照组比较差异有统计学意义（P〈0．05）。高蛋氨酸组血清乳酸脱氢酶、羟丁酸脱氢酶和肌酸激酶及肌酸激酶同工酶含量较正常对照组明显增高，在添加叶酸及维生素B12的干预组中血清肌酸激酶、肌酸激酶同工酶和羟丁酸脱氢酶含量较高蛋氨酸组降低。实时定量PCR结果显示高蛋氨酸组P53mRNA表达上调，免疫组织化学法检测P53蛋白的表达与其mRNA表达变化一致。P53表达与血清肌酸激酶含量呈正相关（r=0．7061，P〈0．01）。结论HHcy可引起ApoE-/-鼠心肌酶谱发生改变．其机制可能与同型半胱氨酸导致的氧化应激有关。这种改变与P53的表达呈正相关，P53亦可能参与其病理过程。补充叶酸及维生素B12对于食饵性HHcy具有良好的治疗效用。

英文摘要：

Aim To explore the effect of hyperhomocysteinemia （HHcy） on the changes of myocardial enzyme spectrum and its correlation with P53 gene. Methods 36 male ApoE -/- mice were randomly divided into 3 groups （ n = 12 for each group） ： AopE -/- control group, hyperhomocysteinemia group and intervention group. They were respectively fed with nomal diet, normal diet enriched 1.7% methionine and nomal diet plus 1.7% methionine 0. 006% folate and 0. 000 4% vitamin B12 for 14 weeks. 12 healthy 5-week-old male C57BL/6J mice were taken as normal control group. The levels of serum homocysteine （Hcy） and myocardial enzyme levels in the four groups were measured by auto- matic biochemical analyzer. The content of serum oxidized low density lipoprotein （ox-LDL） was detected by enzymelinked immunosorbent assay （ELISA） ; the protein and mRNA expressions of P53 in the heart were detected by immunohis tochemical assay and real time polymerase chain reaction （RT-PCR）. Results The content of Hcy was significantly higher in ApoE-/- control group, HHcy group and folate treatment group than normal control group, a remarkable increase was observed in the HHcy mice （P 〈 0. 01 ）, the ox-LDL level showed a parallel increase with the Hcy, the difference was significant （P 〈 0. 05 ）. The contents of creatine kinase-MB （CK-MB）, creatine kinase （CK）, hydroxy butyrate dehydrogenase （HBDH） and lactate dehydrogenase （LDH） were increased significantly in HHcy group while folate and vitamin B12 decreased serum CK-MB, CK and HBDH levels compared with HHcy group. The results of RT-PCR and immunohisto- chemical assay exposed an up-expressed P53 mRNA and protein in HHcy group. The changes of P53 mRNA and serum CK levels had positive correlation （ r = 0. 706 1, P 〈 0. 01 ）. Conclusions Hyperhomocysteinemia could result in the changes of myocardial enzyme spectrum, the homocysteine-induced oxidative stress might be its major pathogenic mechanism. The up-expressed P53 might also be involved in its p