本文關(guān)鍵詞： 高脂喂食 收縮壓 一氧化氮 內(nèi)皮型一氧化氮合酶 非對稱性二甲基精氨酸 二甲基精氨酸二甲胺水解酶　出處：《中華高血壓雜志》2017年09期 　論文類型：期刊論文

【摘要】：目的探討圍產(chǎn)期高脂喂食對雄性子代大鼠腸系膜動脈二甲基精氨酸二甲胺水解酶2(DDAH2)啟動子甲基化水平的影響及在動脈血壓增高中的作用。方法 SD大鼠分為正常脂肪喂食組(NFD)和高脂喂食組(HFD),圍產(chǎn)期分別給予標(biāo)準(zhǔn)飼料(含4.43%脂肪)和高脂飼料(含30%脂肪)喂養(yǎng),分娩后各組隨機(jī)選擇9只雄性子鼠以標(biāo)準(zhǔn)飼料喂養(yǎng),18周齡時采用無創(chuàng)性尾套法測量子鼠動脈血壓水平,檢測腸系膜動脈內(nèi)皮依賴性舒張功能,采用硝酸還原酶法檢測腸系膜動脈一氧化氮含量,酶聯(lián)免疫吸附試驗(yàn)法檢測非對稱性二甲基精氨酸(ADMA)含量及內(nèi)皮型一氧化氮合酶(eNOS)活性,實(shí)時熒光定量聚合酶鏈反應(yīng)(PCR)檢測DDAH2mRNA表達(dá)水平,Western-blot方法檢測DDAH2蛋白表達(dá)水平,巢式甲基化PCR法檢測DDAH2啟動子甲基化水平。結(jié)果與NFD組相比,HFD組子代大鼠收縮壓升高[(143.3±2.6)比(121.7±3.8)mm Hg,P0.05];腸系膜動脈血管環(huán)的舒張百分比降低(均P0.05),敏感性降低(pD2:NFD 6.44±0.18比HFD 7.56±0.26,P0.05);腸系膜動脈一氧化氮含量降低[(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];腸系膜動脈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),啟動子甲基化水平升高(1.20±0.03比0.98±0.04,P0.01)。結(jié)論圍產(chǎn)期高脂喂食可以導(dǎo)致雄性子代大鼠腸系膜動脈DDAH2啟動子甲基化水平增高,引起DDAH2/ADMA/eNOS/一氧化氮通路障礙,是其成年后動脈血壓升高的原因之一。
[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 鹵2.6], the diastolic percentage of mesenteric artery rings was decreased (P0.05a, sensitivity was lower than that of HFD 7.56 鹵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 鹵0.01) compared with 0.53 鹵0.01) 渭 mol 路g / g P0.01] the activity of Enos decreased [0.57 鹵0.01) than 0.73 鹵0.01kUU / g propanP0.01] the content of ADMA increased [0.32 鹵0.07 vs 0.29 鹵0.01], and the decrease of DDAH2mRNA in mesenteric artery was 0.12 鹵0.01 vs 0.15 鹵0.01P0.01P0.01P0.01P 0.01. the level of promoter methylation increased by 1.20 鹵0.03 vs 0.98 鹵4P0.01P 0.01a conclusion: the mesenteric artery DDAH2mRNA decreased by 0.12 鹵0.01 vs 0.15 鹵0.01P0.01P0.01. conclusion the level of promoter methylation increased by 1.20 鹵0.03 vs 0.98 鹵4P0.01P 0.01P 0.01. Conclusion: the mesenteric artery DDAH2mRNA decreased by 0.12 鹵0.01 vs 0.15 鹵0.01 渭 mol 路g / g P0.01 respectively, and the level of promoter methylation increased by 1.20 鹵0.03 vs 0.98 鹵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.
【作者單位】： 山西醫(yī)科大學(xué)汾陽學(xué)院統(tǒng)計(jì)學(xué)教研室;山西醫(yī)科大學(xué)附屬汾陽醫(yī)院心血管內(nèi)科;山西醫(yī)科大學(xué)汾陽學(xué)院生理學(xué)教研室;
【分類號】：R714.7

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