HECTD1激活mTOR信号促进心肌细胞肥大的机制研究  

Study on the mechanism of HECTD1 promoting myocardial hypertrophy by activating mTOR signal pathway

作　　者：焦薇 郭娜[3] 祖秀光[1] 郝杰[1] 孟明杰 谢亚囡[1] 高伟年[2] JIAO Wei;GUO Na;ZU Xiuguang(不详;Department of Cardiology,The Second Hospital of Hebei Medical University,Hebei,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院心血管内三科,石家庄市050000 [2]河北医科大学第二医院心脏大血管外科,石家庄市050000 [3]河北省石家庄市中医院心病一科

出　　处：《河北医药》2022年第15期2280-2283,共4页Hebei Medical Journal

摘　　要：目的探讨含与E6-AP羧基末端同源结构域的E3泛素化蛋白连接酶1(HECT Domain E3 Ubiquitin Protein Ligase 1,HECTD1)在心肌细胞肥大过程中的功能与分子机制。方法选取心肌肥厚患者和对照心肌组织,荧光定量PCR分析心肌肥厚标志基因和HECTD1表达水平。在新生大鼠原代心肌细胞中用siRNA干扰HECTD1,用qRT-PCR和Western blot验证。利用血管紧张素Ⅱ在心肌细胞中诱导心肌肥厚,分析心肌细胞大小和肥厚标志基因表达。利用Western blot检测哺乳动物雷帕霉素受体(mammalian target of rapamycin,mTOR)信号通路激活情况。结果在心肌肥厚患者心肌组织中肌凝蛋白重链7(myosin heavy chain 7,MYH7)、心房钠尿肽(natriuretic peptide A,ANP)和利尿钠肽(natriuretic peptide B,BNP)的表达增加,同时HECTD1表达水平增加。在血管内紧张素Ⅱ诱导的心肌肥厚大鼠心脏中,ANP、BNP、MYH7和HECTD1表达水平增加。siRNA敲低HECTD1表达可以抑制血管紧张素Ⅱ诱导的心肌细胞肥大和心肌肥厚标志基因ANP、BNP和MYH7的表达水平。敲低Hectd1表达可以抑制血管紧张素Ⅱ诱导的mTOR信号通路活性。结论HECTD1通过激活mTOR信号通路促进血管紧张素Ⅱ诱导的心肌细胞肥大。Objective To investigate the effects and effects and molecular mechanism of HECT Domain E3 Ubiquitin Protein Ligase 1(HECTD1)during cardiomyocyte hypertrophy.Methods The myocardial tissues from patients with cardiac hypertrophy and those from controls were collected.The expression levels of hypertrophic genes and HECTD1 were detected by Realtime polymerase chain reaction(RT-PCR).And siRNA was used to knock down the expressions of Hectd1 in primary cardiomyocytes of neonatal rats,which were validated by qRT-PCR and Western Blot.AngiotensinⅡwas used to induce hypertrophy in cardiomyocytes and qRT-PCR was used to analyze the expression of hypertrophic fetal genes.Moreover Western Blot was used to detect the activation of mTOR signaling pathway.Results The expression levels of hypertrophic fetal genes ANP(atrial natriuretic peptide),MYH7(myosin heavy chain 7),BNP(brain natriuretic peptide)and HECTD1 were increased in myocardial tissues of patients with myocardial hypertrophy.The expression levels of ANP,BNP,MYH7 and HECTD1 in heart tissues of rat with myocardial hypertrophy induced by angiotensinⅡ.Moreover siRNA-mediated knockdown of HECTD1 expression inhibited the expression levels of ANP,BNP and MYH7 in angiotensinⅡ-induced cardiomyocyte,and knockdowning the expression of Hectd1 could inhibit the activation of mTOR-S6K signaling pathway induced by angiotensinⅡ.Conclusion HECTD1 can promote the progress of angiotensinⅡ-induced cardiomyocyte hypertrophy by activating the mTOR signaling pathway.

关 键 词：心肌病 肥厚性 血管紧张素Ⅱ 实时聚合酶链反应 

分 类 号：R542.2[医药卫生—心血管疾病]