肠系膜动脉二甲基精氨酸二甲胺水解酶2甲基化在围产期高脂喂食雄性子代大鼠血压升高中的作用

发布时间：2018-02-09 03:15

本文关键词： 高脂喂食收缩压一氧化氮内皮型一氧化氮合酶非对称性二甲基精氨酸二甲基精氨酸二甲胺水解酶　出处：《中华高血压杂志》2017年09期 　论文类型：期刊论文

【摘要】：目的探讨围产期高脂喂食对雄性子代大鼠肠系膜动脉二甲基精氨酸二甲胺水解酶2(DDAH2)启动子甲基化水平的影响及在动脉血压增高中的作用。方法 SD大鼠分为正常脂肪喂食组(NFD)和高脂喂食组(HFD),围产期分别给予标准饲料(含4.43%脂肪)和高脂饲料(含30%脂肪)喂养,分娩后各组随机选择9只雄性子鼠以标准饲料喂养,18周龄时采用无创性尾套法测量子鼠动脉血压水平,检测肠系膜动脉内皮依赖性舒张功能,采用硝酸还原酶法检测肠系膜动脉一氧化氮含量,酶联免疫吸附试验法检测非对称性二甲基精氨酸(ADMA)含量及内皮型一氧化氮合酶(eNOS)活性,实时荧光定量聚合酶链反应(PCR)检测DDAH2mRNA表达水平,Western-blot方法检测DDAH2蛋白表达水平,巢式甲基化PCR法检测DDAH2启动子甲基化水平。结果与NFD组相比,HFD组子代大鼠收缩压升高[(143.3±2.6)比(121.7±3.8)mm Hg,P0.05];肠系膜动脉血管环的舒张百分比降低(均P0.05),敏感性降低(pD2:NFD 6.44±0.18比HFD 7.56±0.26,P0.05);肠系膜动脉一氧化氮含量降低[(0.42±0.01)比(0.53±0.01)μmol/g,P0.01],eNOS活性降低[(0.57±0.01)比(0.73±0.01)kU/g pro,P0.01],ADMA含量增加[(0.32±0.07)比(0.29±0.01)μmol/g pro,P0.05];肠系膜动脉DDAH2mRNA降低(0.12±0.01比0.15±0.01,P0.01),DDAH2蛋白降低(0.24±0.01比0.28±0.01,P0.01),启动子甲基化水平升高(1.20±0.03比0.98±0.04,P0.01)。结论围产期高脂喂食可以导致雄性子代大鼠肠系膜动脉DDAH2启动子甲基化水平增高,引起DDAH2/ADMA/eNOS/一氧化氮通路障碍,是其成年后动脉血压升高的原因之一。
[Abstract]:Objective to investigate the effect of perinatal hyperlipidemia on methylation of the promoter of dimethyl arginine dimethylamine hydrolase 2DDAH2 in the mesenteric artery of male offspring rats and its role in the elevation of arterial blood pressure. Methods SD rats were divided into normal rats. During perinatal period, standard diet (containing 4.43% fat) and high fat diet (containing 30% fat) were given to the fat feeding group and the high fat feeding group respectively, while the high fat feeding groups were fed with standard diet (containing 4.43% fat) and high fat diet (containing 30% fat) during the perinatal period. After delivery, nine male offspring were randomly selected to be fed with standard diet for 18 weeks to measure the blood pressure of the quantum rat artery and the endothelium-dependent relaxation function of the mesenteric artery at the age of 18 weeks. The content of nitric oxide in mesenteric artery was detected by nitrate reductase method, the content of asymmetric dimethyl arginine (ADMA) and the activity of endothelial nitric oxide synthase (Enos) in mesenteric artery were detected by enzyme-linked immunosorbent assay (Elisa). Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the expression of DDAH2mRNA and Western-blot was used to detect the expression of DDAH2 protein. Results compared with the NFD group, the systolic blood pressure (SBP) was increased [143.3 卤2.6], the diastolic percentage of mesenteric artery rings was decreased (P0.05a, sensitivity was lower than that of HFD 7.56 卤0.26P0.05P, P < 0.05). The methylation level of DDAH2 promoter was detected by nested methylation PCR method in comparison with that in NFD group (P < 0.05). The systolic blood pressure was higher than that in NFD group (P < 0.05), and the diastolic percentage of mesenteric artery rings was significantly lower than that in NFD group (P < 0.05), and the sensitivity was significantly lower than that in HFD group (P < 0.05). The content of nitric oxide in mesenteric artery decreased [0.42 卤0.01) compared with 0.53 卤0.01) 渭 mol 路g / g P0.01] the activity of Enos decreased [0.57 卤0.01) than 0.73 卤0.01kUU / g propanP0.01] the content of ADMA increased [0.32 卤0.07 vs 0.29 卤0.01], and the decrease of DDAH2mRNA in mesenteric artery was 0.12 卤0.01 vs 0.15 卤0.01P0.01P0.01P0.01P 0.01. the level of promoter methylation increased by 1.20 卤0.03 vs 0.98 卤4P0.01P 0.01a conclusion: the mesenteric artery DDAH2mRNA decreased by 0.12 卤0.01 vs 0.15 卤0.01P0.01P0.01. conclusion the level of promoter methylation increased by 1.20 卤0.03 vs 0.98 卤4P0.01P 0.01P 0.01. Conclusion: the mesenteric artery DDAH2mRNA decreased by 0.12 卤0.01 vs 0.15 卤0.01 渭 mol 路g / g P0.01 respectively, and the level of promoter methylation increased by 1.20 卤0.03 vs 0.98 卤4P0.01respectively. Feeding on mesenteric artery DDAH2 promoter increased the methylation level of mesenteric artery promoter in male offspring rats. The dysfunction of DDAH _ 2 / ADMA / eNOS / nitric oxide pathway is one of the reasons for the rise of arterial blood pressure in later adulthood.
【作者单位】：山西医科大学汾阳学院统计学教研室;山西医科大学附属汾阳医院心血管内科;山西医科大学汾阳学院生理学教研室;
【分类号】：R714.7

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