血管紧张素Ⅱ1型受体自身抗体在甲亢大鼠心肌肥大的作用及与微小RNA-350的相关性研究

Analysis on angiotensin Ⅱ type 1 receptor agonistic autoantibody in hyperthyroidism rats associated with cardiac hypertrophy and its relationship with microRNA-350

本研究旨在探讨血管紧张素Ⅱ1型受体自身抗体(AT1-AA)在甲亢大鼠心肌肥大的表达及其与miRNA-350关系。将36只健康SD大鼠随机分为正常组及甲亢组,采用病理学、ELISA、RT-PCR和western blot等方法,比较甲亢组及对照组大鼠心肌肥大指标、AT1-AA、miRNA-350、AT1R mRNA及蛋白的表达;进一步将甲亢大鼠按AT1-AA检测结果分为AT1-AA阳性组和阴性组,比较两组miRNA-350、AT1R mRNA及蛋白的表达。结果显示,甲亢大鼠心肌肥大指标较正常大鼠均明显升高,且甲亢大鼠AT1-AA阳性率及A值明显高于对照组大鼠。甲亢组大鼠miRNA-350及AT1R的表达明显高于正常对照组,并深入研究发现AT1-AA阳性组miRNA-350及AT1R的表达亦高于AT1-AA阴性组。上述结论表明,AT1-AA参与甲亢大鼠心肌肥大的病理生理过程,miRNA-350在甲亢心肌肥大时AT1-AA的产生中发挥关键作用。

The present study aims to explore the expression of angiotensin Ⅲ type 1 receptor agonistic autoantibody （AT^-AA） in hyperthyroidism rats associated with cardiac hypertrophy and its relationship with miRNA-350. Thirty-six SD rats were ran- domly divided into control group and hyperthyroidism group. Using pathology, ELISA, RT-PCR and Western blotting meth- ods, indexes of cardiac hypertrophy, serum AT1-AA, miRNA-350, mRNA and protein of angiotensin II type 1 receptor （AT1R） were compared between hyperthyroidism rats and the control rats. Hyperthyroidism rats were subdivided into AT1- AA positive group and negative group based on the levels of AT1-AA. The expression of miRNA-350 and ATI R were com- pared between these two groups. The results showed that, compared with the normal controls, rats with hyperthoidism group showed higher cardiac indexes, higher rate of AT1-AA positivity as well as higher A value. Besides, expression of miRNA-350 and AT1R were markedly higher in the diseased rats, compared with the normal rats. Furthermore, when AT1-AA positive group was compared with AT1-AA negative group, miRNA-35 and AtlR levels were significantly elevated. These results indi- cate that serum AT^-AA maybe involved in the pathogenesis of cardiac hypertrophy in hyperthyroidism, and miRNA-350 could play an important role in the production of AT1-AA.