ERRα通过AKT/SGK1通路抑制盐敏感性高血压大鼠的盐敏感性

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英文篇名：ERRα inhibits salt sensitivity of salt-sensitive hypertensive rats via AKT/SGK1 pathway 作者：任洁 ; 胡经文 ; 郭统帅 ; 何明俊 ; 刘富强 ; 牟建军 英文作者：REN Jie;HU Jingwen;GUO Tongshuai;HE Mingjun;LIU Fuqiang;MOU Jianjun;Department of Cardiovascular Medicine,First Affiliated Hospital of Xi'an Jiaotong University,Key Laboratory of Molecular Cardiology of Shaanxi Province,Key Laboratory of the Ministry of Environment and Disease-related Education;Department of Cardiology,Shaanxi People's Hospital; 关键词：雌激素相关受体α ; 盐敏感性大鼠 ; 盐敏感性高血压 ; 氧化应激 ; AKT/SGK1通路 英文关键词：ERRα;;salt-sensitive rats;;salt-sensitive hypertension;;oxidative stress;;AKT/SGK1 pathway 中文刊名：SXYX 英文刊名：Journal of Shanxi Medical University 机构：西安交通大学第一附属医院心血管内科陕西省分子心脏病学重点实验室环境与疾病相关教育部重点实验室;陕西省人民医院心内科; 出版日期：2019-04-22 15:52 出版单位：山西医科大学学报 年：2019 期：v.50;No.318 基金：陕西省自然科学基础研究计划项目(2017JM8157) 语种：中文; 页：SXYX201904002 页数：5 CN：04 ISSN：14-1216/R 分类号：11-15

摘要

目的探讨雌激素相关受体α(ERRα)对盐敏感性高血压大鼠盐敏感性的影响及分子机制。方法 6周龄雄性ERRα过表达及其对照Dahl盐敏感性大鼠分为四组,分别为正常盐对照组、正常盐ERRα过表达组、高盐对照组和高盐ERRα过表达组。正常盐对照组和正常盐ERRα过表达组大鼠每天给予正常盐(含氯化钠0. 5%)饲料喂养,高盐对照组和高盐ERRα过表达组大鼠每天给予高盐(含氯化钠8%)饲料喂养,大鼠被喂养3周,然后检测大鼠血压以及血液SOD和MDA水平;通过实时荧光定量PCR和Western blot检测盐敏感性高血压大鼠胸主动脉ERRα的m RNA表达以及AKT和SGK1磷酸化水平。结果荧光定量PCR结果显示,与正常盐对照组相比,高盐对照组大鼠中ERRα相对表达量显著降低(P <0. 01)。与高盐对照组比较,高盐ERRα过表达组大鼠血压显著降低,血液SOD活性显著升高,MDA含量显著降低(均P <0. 01)。Western blot结果显示,高盐ERRα过表达组大鼠p-AKT和p-SGK1蛋白表达显著高于高盐对照组,差异具有统计学意义(均P <0. 01)。结论 ERRα通过AKT/SGK1通路抑制盐敏感性高血压大鼠氧化应激,降低大鼠盐敏感性。
        Objective To investigate the effect of estrogen-related receptors α( ERRα) on salt sensitivity in salt-sensitive hypertensive rats and its molecular mechanism. Methods Six-week-old male ERRα overexpression and control Dahl salt-sensitive rats were divided into four groups: normal salt control group,normal salt ERRα overexpression group,high salt control group and high salt ERRαoverexpression group. The rats were fed with normal salt( containing 0. 5% Na Cl) diet per day in normal salt control group and normal salt ERRα overexpression group,and high salt( containing 8% Na Cl) diet per day in high salt control group and high salt ERRα overexpression group. Rats were fed for 3 weeks and then the blood pressure,blood SOD and MDA levels were measured. The m RNA expression of ERRα and the phosphorylation levels of AKT and SGK1 in thoracic aorta of salt-sensitive hypertensive rats were detected by real-time fluorescent quantitative PCR and Western blot,respectively. Results Compared with normal salt control group,the expression of ERRα was significantly decreased in high salt control group( all P < 0. 01). Compared with high-salt control group,the blood pressure was significantly decreased in high-salt ERRα overexpression group,blood SOD activity was significantly increased,and MDA content was significantly decreased( all P < 0. 01). In addition,the expression of p-AKT and p-SGK1 protein in high salt ERRα overexpression group was significantly higher than that in high salt control group( all P < 0. 01). Conclusion ERRα may inhibit oxidative stress in salt-sensitive hypertensive rats and reduce salt sensitivity in rats via AKT/SGK1 pathway.

引文

[1]Wang K,Chu C,Hu J,et al.Effect of salt intake on the serum cardiotrophin-1 levels in Chinese adults[J].Ann Nutr Metab,2018,73(4):302-309.
    [2]Kardos M,Masura J.Spontaneous regression of multiple pulmonary aneurysms in a patient with midaortic syndrome and arterial hypertension[J].Bratisl Lek Listy,2016,117(2):119-120.
    [3]Waghulde H,Cheng X,Galla S,et al.Attenuation of microbiotal dysbiosis and hypertension in a CRISPR/Cas9 gene ablation rat model of GPER1[J].Hypertension,2018,72(5):1125-1132.
    [4]Li D,Wang Q,Zhang Y,et al.A novel swine model of spontaneous hypertension with sympathetic hyperactivity responds well to renal denervation[J].Am J Hypertens,2016,29(1):63-72.
    [5]Nagayoshi S,Ogawa A,Matsubara H.Spontaneous enlargement of pulmonary artery after successful balloon pulmonary angioplasty in a patient with chronic thromboembolic pulmonary hypertension[J].EuroIntervention,2016,12(11):e1435.
    [6]Park WC.Role of ovarian function suppression in premenopausal women with early breast cancer[J].J Breast Cancer,2016,19(4):341-348.
    [7]Chantakat E,Boudou F,Laurell H,et al.The AF-1-deficient estrogen receptor ERα46 isoform is frequently expressed in human breast tumors[J].Breast Cancer Res,2016,18(1):123.
    [8]Niv Y.Estrogen receptorβexpression and colorectal cancer:a systematic review and meta-analysis[J].Eur J Gastroenterol Hepatol,2015,27(12):1438-1442.
    [9]Wang D,Wang Y,Liu FQ,et al.High salt diet affects renal sodium excretion and ERRαexpression[J].Int J Mol Sci,2016,17(4):480.
    [10]Sun L,Fan H,Yang L,et al.Tyrosol prevents ischemia/reperfusion-induced cardiac injury in H9c2 cells:involvement of ROS,Hsp70,JNK and ERK,and apoptosis[J].Molecules,2015,20(3):3758-3775.
    [11]Wang Y,Sun Z,Chen S,et al.ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic effect of ajoene on cells of lung adenocarcinoma[J].Tumour Biol,2016,37(3):3727-3738.
    [12]Qi D,He J,Wang D,et al.17β-estradiol suppresses lipopolysaccharideinduced acute lung injury through PI3K/Akt/SGK1mediated up-regulation of epithelial sodium channel(ENaC)in vivo and in vitro[J].Respir Res,2014,15:159-171.