ERRα通过AKT/SGK1通路抑制盐敏感性高血压大鼠的盐敏感性

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.