摘要
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。
Aim To explore the role of serum S-adenosylmethionine （SAM）/S-adenosylhomo cysteine （SAH） in vascular atherosclerosis B1 repetitive sequence DNA methylation induced by Hcy in ApoE / mice. Methods 36 male Apo E-/- mice fed for 4 months were randomly divided into 3 groups： model control group, high methionine group and folic acid＋VitB12 intervention group, 12 mice in each group, and they were respectively fed with different diets. 12 healthy 4-week-old male C57BL/6J mice were taken as normal control group which were fed with normal diet for 15 weeks. The atheromatous plaque were detected by HE staining, the levels of SAM and SAH in the serum were detected by high performance liquid chromatography （HPLC） and the methylation levels of B1 repetitive sequences by methylmion specific PCR （MSP）. Results Compared with the normal control group, serum Hcy levels of high methionine group were significantly increased by 2.39 fold （P〈0.01）. The arterio-plaque formed in the high methionine group by HE staining. The expression of SAM/SAH increased by 1.68 and 2.75 fold in the model control group and the high methionine group （ P 〈0.01）. Compared with the normal control group, the methylation levels of B1 repetitive sequences significantly decreased 11.8% in the high methionine group （P〈0.05）, and had negative correlation with SAM/SAH（r=-0.3638,P=0.0210）.Conclusion B1 repetitive sequences in ApoE / mice had DNA low methylation and it was negatively correlated with SAM/SAH, which suggested that serum SAM/SAH could be used as a biological index to determine vascular As.
作者
张辉
郭伟
高婷婷
马燕琼
惠淑宁
马胜超
杨晓玲
蒋袁絮
田珏
姜怡邓
ZHANG Hui GUO Wei GAO Ting-Ting MA Yan-Qiong HUI Shu-Ning MA Sheng-Chao YANG Xiao-Ling JIANG Yuan-Xu TIAN Jue JIANG Yi-Deng(Department of Clinical Medicine Department of Preclinical Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China)
出处
《中国动脉硬化杂志》
CAS
北大核心
2017年第2期129-133,共5页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金资助项目(81360063和81560242)
宁夏教育厅资助项目(NGY2015092)
