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目的探讨血清S-腺苷甲硫氨酸(SAM)/S-腺苷同型半胱氨酸(SAH)比值在同型半胱氨酸(Hcy)致载脂蛋白E基因敲除(Apo E―/―)小鼠血管动脉粥样硬化(As)B1重复序列DNA甲基化改变中的作用。方法 36只饲养4周龄Apo E―/―小鼠,随机分为三组:模型对照组、高蛋氨酸组、叶酸+Vit B12干预组,每组12只,分别给予不同饮食;另取健康4周龄雄鼠(SPF级C57BL/6J)12只作为正常对照组,饲以普通饮食。饲养15周后,HE染色观察血管内动脉斑块的形成,高效液相色谱检测血清中Hcy、SAM、SAH的水平改变,n MS-PCR检测各组小鼠动脉粥样硬化斑块中Bl重复序列DNA甲基化改变。结果高蛋氨酸组血清Hcy与正常对照组相比升高约2.39倍(P<0.01),HE染色可见高蛋氨酸组中有动脉斑块形成;与正常对照组相比,模型对照组、高蛋氨酸组SAM/SAH增加了1.68倍和2.75倍(P<0.01);高蛋氨酸组B1重复序列DNA甲基化水平降低11.8%(P<0.05),且与SAM/SAH比值呈明显负相关(r=-0.3638,P=0.0210)。结论 ApoE―/―小鼠中B1重复序列发生DNA低甲基化改变,且与SAM/SAH呈负相关,提示血清SAM/SAH可作为一个判断血管As的生物学指标。
Objective To investigate the relationship between the ratio of serum S-adenosylmethionine (SAM) / S-adenosylhomocysteine (SAH) and apolipoprotein E knockout (Apo E- / -) mouse vascular atherosclerosis (As) B1 repeat DNA methylation changes in the role. Methods Thirty-six Apo E - / - mice, aged 4 weeks, were randomly divided into three groups: model control group, high methionine group and folic acid + Vit B12 intervention group, with 12 rats in each group. Twelve weeks old male rats (SPF grade C57BL / 6J) were used as normal control group and fed with normal diet. After 15 weeks of feeding, the formation of intravascular plaque was observed by HE staining. The levels of Hcy, SAM and SAH in serum were detected by high performance liquid chromatography (HPLC), and the level of Hcy, SAM and SAH in the mice were detected by n MS-PCR DNA methylation changes. Results The level of Hcy in high methionine group was about 2.39 times higher than that of the normal control group (P <0.01), and the formation of arterial plaque in high methionine group was observed by HE staining. Compared with the normal control group, the model control group, the high methionine group SAM / SAH increased 1.68-fold and 2.75-fold, respectively (P <0.01). DNA methylation level of B1 repeat in high methionine group decreased by 11.8% (P <0.05) and negatively correlated with SAM / 0.3638, P = 0.0210). Conclusions The DNA hypomethylation of B1 repeat in ApoE - / - mice was negatively correlated with SAM / SAH, suggesting that serum SAM / SAH could be used as a biological marker for judging vascular As.