| 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/p-Akt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。 |
| 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 |
| DOI：10.3724/SP.J.1008.2014.00154 |
| 投稿时间：2013-06-20修订日期：2013-07-15 |
| 基金项目:武汉市科技局科研项目（2013060602010244）. |
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| Role of angiotensin Ⅱ type 1 receptor agonistic autoantibody in cardiac hypertrophy of hyperthyroidism rats and its relationship with PI3K/Akt signaling pathway |
| XU Jin-ling1,ZHAO Lin-shuang1*,WANG Min2 |
(1. Department of Endocrinology and Metabolism, Wuhan General Hospital, PLA Guangzhou Military Area Command, Wuhan 430070, Hubei, China;
2. Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China
*Corresponding author.) |
| Abstract: |
| 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 were subdivided into AT1-AA positive group and negative group; the expressions of AT1R and PI3K/Akt were compared between these groups. Results (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 significantly decreased than those in AT1-AA negative group (P<0.05). Conclusion AT1-AA may be involved in the pathophysiology of cardiac hypertrophy in hyperthyroidism by activating PI3K/Akt signaling pathway through AT1R. |
| Key words: angiotensin Ⅱ type 1 receptor autoantibodies Akt hyperthyroidism Cardiac hypertrophy |
