钠、钾干预对Dahl盐敏感大鼠血管内皮非对称性二甲基精氨酸水平的影响及机制  

Effect of dietary sodium and potassium intervention on the expression of asymmetric dimethylarginine in Dahl salt-sensitive rats and its mechanism

作　　者：王丹[1] 方媛[1] 牟建军[1] 曹禺[1] 高卫华[1] 刘富强[1] 郭会[1] 廉秋芳[1] 郑树惠 

机构地区：[1]西安交通大学第一附属医院心内科,陕西西安710061

出　　处：《中华高血压杂志》2014年第9期847-851,共5页Chinese Journal of Hypertension

基　　金：国家自然科学基金(30900616)

摘　　要：目的通过给予Dahl盐敏感性(SS)大鼠及SS.13BN大鼠高盐、高盐补钾饲料,观察钠、钾干预对主动脉内皮非对称性二甲基精氨酸(ADMA)生成及代谢相关激酶[蛋白质精氨酸甲基转移酶Ⅰ(PRMT-Ⅰ)和二甲基精氨酸二甲胺水解酶Ⅱ(DDAH-Ⅱ)]的影响,探讨盐敏感性大鼠内皮功能紊乱以及补钾对内皮的保护机制。方法 8周龄SS雄性大鼠和SS.13BN雄性大鼠各27只分别随机分为正常盐组、高盐组、高盐补钾组,干预8周,每组9只;干预前后测量大鼠体质量,并采用MODEL-229动物无创血压测定仪测量血压;腹主动脉取血,采用高效液相法测量血清ADMA浓度;取主动脉,采用RT-PCR和Western blot法从mRNA和蛋白水平上对主动脉内皮中PRMT-Ⅰ和DDAH-Ⅱ的表达进行检测。结果 1给予高盐饲料干预后,SS大鼠血压高于SS.13BN大鼠[(164±5)比(156±3)mm Hg,P<0.05];SS大鼠高盐补钾组血压低于其高盐组水平[(150±11)比(164±5)mm Hg,P<0.05]。2SS大鼠高盐干预后,血清ADMA浓度高于正常盐组[(74.5±10.8)比(62.0±5.6)mg/L,P<0.05],补钾后低于高盐组[(64.5±4.7)比(74.5±10.8)mg/L,P<0.05]。3SS高盐组大鼠主动脉PRMT-Ⅰ的蛋白含量高于正常盐组(P<0.05),但补钾可逆转上述作用(P<0.05)。4高盐干预后,SS大鼠主动脉DDAH-Ⅱ的mRNA水平低于正常盐组(P<0.05),而补钾可增加DDAH-Ⅱ的表达(P<0.05)。结论高盐介导的SS大鼠血压升高可能与体内PRMT-Ⅰ/ADMA/DDAH-Ⅱ生成代谢紊乱有关,而补钾可能通过纠正该紊乱发挥降压及血管保护的作用。Objective To observe the effects o：f sodium and potassium intervention on the generation of asymmetric dimethylarginine （ADMA） and metabolism-associated kinase [protein-arginine methyhransferases-Ⅰ （PRMT-Ⅰ） ＆ dimethylarginine dimethylamine hydrolase- Ⅱ （DDAH- Ⅱ）] and explore the mechanism of potassium supplementation in Dahl salt-sensitive rats and SS. 13BN rats having high-sodium diets and high-salt diets with potassium supplemen- tation. Methods Twenty-seven male SS rats and twenty-seven male SS. 13BN rats, all 8-week-old, were randomly divided into three groups respectively： normal salt group （NS, n= 9}, high-sah group （HS, n= 9） and high-salt with potassium supplementation group （HSK, n= 9）. The diet intervention experiment lasted for 8 weeks. The rats＇ weight was measured before and after the intervention, and blood pressure determined by noninvasive blood pressure measurement devices. Blood was collected from abdominal aorta and serum ADMA was measured by high- performance liquid chromatography. The aorta was collected, and the mRNA and protein expression of PRMT-Ⅰ and DDAH- Ⅱ in aortic endothelium were detected by real time polymerase chain reaetion （RT-PCR） and Western blot. Results The blood pressure of SS rats was higher than that of SS. 13BN rats in each HS group [（164±5） vs （156±3）mm Hg, P〈0.051, whereas the blood pressure of SS rats in HSK group was lower than that in HS group [ （150±11） vs （164±5）mm Hg, P〈0.05]. The concentration of serum ADMA of SS rats in HS group was higherthan that in NS group [（74.5±10.8） vs （62.0±5.6）mg/L, P〈0.05], while the serum ADMA level of SS rats in HSK group was lower than that in HS group [（64.5±4.7） vs （74.5±10.8）mg/L, P〈0.05]. The protein con- tent of SS rats＇ aortic PRMT-Ⅰ in HS group was higher than that in NS group （P〈0.05）, which could be reversed by potassium supplementation （P〈0.05）. The mRNA expression of DDAH-11 of SS rats in HS group was lower than t

关 键 词：盐敏感性 非对称性二甲基精氨酸 钠 钾 

分 类 号：R544.1[医药卫生—心血管疾病]