血管紧张素Ⅱ1型受体自身抗体在甲亢大鼠心肌肥大中的作用及其与PI3K/Akt信号通路的关系  

Role of angiotensinⅡtype 1 receptor agonistic autoantibody in cardiac hypertrophy of hyperthyroidism rats and its relationship with PI3K/Akt signaling pathway

作　　者：徐金玲[1] 赵林双[1] 王敏[2] 

机构地区：[1]广州军区武汉总医院内分泌科,武汉430070 [2]华中科技大学同济医学院附属协和医院心血管病研究所,武汉430022

出　　处：《第二军医大学学报》2014年第2期154-160,共7页Academic Journal of Second Military Medical University

基　　金：武汉市科技局科研项目(2013060602010244)~~

摘　　要：目的观察甲亢心肌肥大大鼠血清血管紧张素Ⅱ1型受体自身抗体(AT1-AA)与心肌组织磷脂酰肌醇-3-激酶(PI3K)、蛋白激酶B(Akt)的表达,探讨AT1-AA在甲亢大鼠心肌肥大中的作用及其与PI3K/Akt信号通路的关系。方法将54只SD大鼠随机分为3组:甲亢组、甲亢+奥美沙坦组及对照组,每组18只,前2组灌服左甲状腺素钠制备甲亢大鼠模型,甲亢+奥美沙坦组同时给予奥美沙坦。以心脏质量指数(HWI)和心钠肽(ANP)mRNA作为心肌肥大指标,采用酶联免疫吸附法(ELISA)检测大鼠血清AT1-AA,并通过蛋白质印迹法检测各组大鼠血管紧张素Ⅱ1型受体(AT1R)和PI3K/p-Akt的表达水平;根据AT1-AA检测结果,将甲亢组和甲亢+奥美沙坦组大鼠分为AT1-AA阳性组和阴性组,比较AT1-AA阳性组和阴性组AT1R及PI3K/p-Akt的表达情况。结果 (1)与对照组比较,甲亢组、甲亢+奥美沙坦组大鼠HWI增加,ANP mRNA相对表达量升高(P均<0.05);甲亢组大鼠HWI及ANP mRNA相对表达量亦高于甲亢+奥美沙坦组大鼠(P<0.05)。(2)甲亢组、甲亢+奥美沙坦组大鼠AT1-AA阳性率及光密度(D)值(61.11%,72.22%和0.44±0.12,0.49±0.08)高于对照组(16.67%和0.28±0.05,P均<0.01)。(3)甲亢组、甲亢+奥美沙坦组大鼠AT1R和PI3K/pAkt的表达较对照组升高(P<0.05,P<0.01);与甲亢组相比,甲亢+奥美沙坦组大鼠心肌组织PI3K、p-Akt表达水平均降低(P<0.01,P<0.05)。(4)甲亢组大鼠中,AT1-AA阳性组PI3K/p-Akt的表达明显高于AT1-AA阴性组(P<0.01);甲亢+奥美沙坦组大鼠中,AT1-AA阳性组PI3K/p-Akt的表达较AT1-AA阴性组降低(P<0.05)。结论 AT1-AA可能通过AT1R激活PI3K/Akt信号通路参与甲亢心肌肥大病理生理过程。Objective To investigate the serum level of angiotensin Ⅱ type 1 receptor （AT1R） agonistic autoantibody （AT1-AA） in hyperthyroidism rats with cardiac hypertrophy and the expression of PI3K and protein kinase B （Akt） in cardiac tissue, so as to study the relationship between AT1 AA and PI3K/Akt signaling pathway. Methods Hyperthyroidism rats models were established by gavaging with levothyroxine sodium. Totally 54 SD rats were divided into three groups： hyperthyroidism group（group A）, hyperthyroidism ＋ olmesartan group（group B） and control group （group C）. The heart weight index （HWI） and atrial natriuretic peptide （ANP） mRNA were taken as the indices for cardiac hypertrophy. Serum AT1 AA level was determined by enzyme linked immunosorbent assay （ELISA）, and the expression of AT1R and PI3K/Akt was detected by Western blotting analysis. According to the determination results of AT1-AA, group A and B rats weresubdivided into AT1-AA positive group and negative group; the expressions of AT1R and PI3K/Akt were compared between these groups. Result （1） Compared with group C, HWI and the expression of ANP mRNA in group A and B were significantly increased （all P〈0.05） ; and those in group A were significantly higher than those in group B （P〈0.05）. （2） The positive rates and OD values of AT1-AA in group A and B （61.11%, 72.22% and 0.44±0.12, 0.49± 0.08） were significantly higher than those in group C （16.67% and 0.28±0.05） （all P〈0.01）. （3）The expressions of AT1R and PI3K/p Akt in group A and B were significantly higher than those in group C （P〈0.05, P〈0.01）. Compared with group A, the expression levels of PI3K, p Akt were significantly decreased in group B （P〈0.01, P〈0.05）. （4） In group A, the expression levels of PI3K and p Akt in AT1- AA positive group were significantly higher than those in AT1-AA negative group（P〈0. 01） ; in group B, the expression levels of PI3K and p Akt in AT1-AA positive group were signifi

关 键 词：血管紧张素Ⅱ1型受体 自身抗体 AKT 甲状腺功能亢进 心肌肥大 

分 类 号：R581.1[医药卫生—内分泌]