氯沙坦对自发性高血压大鼠心脏血管紧张素转换酶2-血管紧张素(1～7)-MAS-ERK通路的影响  

The Influence of Losartan on ACE2-Ang(1-7)-MAS-ERK Pathway of Hearts in Spontaneously Hypertensive Rats

作　　者：侯亮[1] 刘雪平[1] 侯训尧[1] 袁树华[1] 徐松[1] 王美霞[1] 

机构地区：[1]山东大学附属省立医院保健神经科,山东济南250021

出　　处：《中华高血压杂志》2010年第2期177-182,共6页Chinese Journal of Hypertension

基　　金：中央保健专项资助课题(鲁A032)

摘　　要：目的探讨氯沙坦对自发性高血压大鼠(SHR)心肌中血管紧张素转换酶2(ACE2)-血管紧张素(1～7)[Ang(1-7)]-MAS-ERK通路的影响。方法30周龄SHR随机分为SHR组(n=11)、氯沙坦组[氯沙坦灌胃30mg/(kg·d),n=12],以Wistar大鼠(WKY)作正常对照(n=12)。处理12周后,应用放射免疫法检测大鼠血浆及心肌组织血管紧张素Ⅱ(AngⅡ)、血管紧张素(1～7)[Ang-(1-7)]水平;采用RT-PCR法检测各组大鼠心肌血管紧张素转换酶(ACE)、ACE2和MAS受体mRNA水平;采用Western blot法检测ACE、ACE2和磷酸化细胞外信号调节激酶(pERK1/2)蛋白表达水平。结果用药12周后,氯沙坦组血压明显低于SHR组[(164.3±21.6)比(241.3±24.5)mmHg,P<0.01];SHR组心肌ACE mRNA和蛋白表达水平显著高于WKY组,而ACE2 mRNA和蛋白表达、心肌MAS受体mRNA表达水平明显低于WKY组,差异有统计学意义(P<0.01);氯沙坦组ACE2 mRNA和蛋白表达、MAS mRNA表达水平高于SHR组(P<0.01),心肌磷酸化ERK1/2蛋白相对水平低于SHR组。结论SHR心肌存在ACE/ACE2比例失衡,血管紧张素受体拮抗剂改善心室重构,可能与ACE2-Ang[(1-7)]-MAS-ERK通路有关。Objective To explore the change of ACE2-Ang（1-7）-MAS-ERK in the heart of spontaneously hypertensive rats and the effect of losartan on this pathway.Methods30-week-old spontaneously hypertensive rats were randomly divided into SHR group （n=11） and losartan group [losartan 30 mg/（kg·d）,n=12], and 12 Wistar rats of the same age served as control.After 12 weeks treatment, the level of Ang Ⅱ, Ang（1-7） in serum and myocardial tissue were detected by radioimmunoassay.The mRNA expression levels of ACE, ACE2 and MAS were detected by RT-PCR respectively.The protein levels of ACE, ACE2 and pERK1/2 in left ventricle were detected by the Western blot.ResultsAfter 12 weeks of medication, the blood pressure in losartan group was lower than that in SHR group [（164.3±21.6）vs（241.3±24.5）mm Hg,P〈0.01].The relative level of myocardial ACE mRNA and protein expression in SHR was significantly higher than WKY group, while the relative expression level of ACE2 mRNA and protein in SHR was significantly lower than the WKY group.The expression of MAS receptor mRNA in SHR group was lower than WKY group.The expression level of ACE2 mRNA and protein in losartan group was higher than that in SHR group.The expression of MAS receptor mRNA in losartan group was higher than SHR（P〈0.01）.The relative level of myocardial pERK1/2 protein in losartan group was lower than the SHR group.ConclusionsThe ratio of ACE/ACE2 was unbalanced in rat of SHR, ACE2-Ang（1-7）-MAS-ERK pathway may play a role in the process of myocardial remodelling in SHR treated by ARB.

关 键 词：自发性高血压 氯沙坦 血管紧张素转换酶2 MAS受体 

分 类 号：R544.1[医药卫生—心血管疾病]