ECE-1基因启动子甲基化调控AKT/eNOS通路对心肌肥厚的影响  被引量:1

Effect and mechanism of ECE-1 gene promoter methylation on cardiac hypertrophy via AKT/eNOS pathway

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作  者:樊琼玲 王家威 刘涛[2] 俞金秀 马正文 由淑萍[1] FAN Qiongling;WANG Jiawei;LIU Tao;YU Jinxiu;MA Zhengwen;YOU Shuping(School of Nursing,Xinjiang Medical University,Urumqi 830011,China;School of Public Health,Xinjiang Medical University,Urumqi 830011,China)

机构地区:[1]新疆医科大学护理学院,乌鲁木齐830011 [2]新疆医科大学公共卫生学院,乌鲁木齐830011

出  处:《新疆医科大学学报》2020年第10期1302-1307,共6页Journal of Xinjiang Medical University

基  金:新疆维吾尔自治区自然科学基金(2018D01C145)。

摘  要:目的探讨压力超负荷心肌肥厚大鼠内皮素转换酶-1(ECE-1)基因启动子的甲基化状态及其调控蛋白激酶B/内皮型一氧化氮合酶(AKT/eNOS)信号通路促进心肌肥厚发病的机制。方法雄性SD大鼠30只随机分成空白组、假手术组、实验组,每组10只。实验组通过腹主动脉缩窄术构建压力超负荷心肌肥厚模型,假手术组分离动脉但不结扎,空白组不手术;第43天检测心重比、心脏超声、心肌形态学改变;RT-qPCR检测心房利钠肽(ANP)和脑利钠肽(BNP)含量;免疫组化法检测ECE-1在心肌组织中的表达;MSP法检测ECE-1基因甲基化状态;Western blot法检测ECE-1、p-AKT、p-eNOS等表达。结果与假手术组比,实验组心重比、左室舒末后壁厚度增加,左室射血分数、左室短轴收缩率减小,形态学观察到实验组心肌明显肥厚(P<0.01),ANP和BNP mRNA表达升高(P<0.01)。与假手术组比,实验组大鼠心肌组织中ECE-1在细胞质表达上调(P<0.01);存在ECE-1非甲基化大鼠的ECE-1蛋白表达上调,p-AKT和p-eNOS蛋白表达下调(P<0.01)。结论压力超负荷心肌肥厚大鼠ECE-1基因启动子的非甲基化可能导致ECE-1表达增加,p-AKT、p-eNOS水平下降,其可能通过抑制AKT/eNO途径促进心肌肥厚的发生。Objective To investigate the methylation status of the endothelin converting enzyme 1(ECE-1)and its mechanism on regulating protein kinase B/endothelial nitric oxide enzyme(AKT/eNOS)signaling pathway to promote the incidence of myocardial hypertrophy.Methods A total of 30 male SD rats were randomly divided into control group,sham group,and test group.Rats in the test group were established with pressure-overload cardiac hypertrophy model by abdominal aortic constriction.The sham group was isolated from the abdominal aorta without ligation.On day 43,heart weight ratio,echocardiography,and myocardial morphology were measured.RT-qPCR was used to detect atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)content.Immunohistochemistry was used to detect ECE-1 expression in myocardial tissue;and MSP was used to detect the methylation status of ECE-1;western blot was used to detect the expression of ECE-1,p-AKT,p-eNOS.Results Compared with the sham group,heart weight ratio in the test group and left ventricular posterior wall thickness were increased,while ejection fraction and fractional shortening were decreased.The morphology of the test group showed significant hypertrophy(P<0.01)and significant increase of ANP and BNP mRNA expression levels(P<0.01).Compared with the sham group,the expression of ECE-1 in the myocardium of the test group was up-regulated in the cell membrane and cytoplasm(P<0.01).There were rats with ECE-1 unmethylation whose expression level of ECE-1 protein was up-regulated,and the expression level of p-AKT and p-eNOS protein was down-regulated(P<0.01).Conclusion Unmethylation of ECE-1 gene promoters in rats with pressure overload myocardial hypertrophy may lead to increased expression of ECE-1,and decreased levels of p-AKT,p-eNOS,which may promote the incidence of myocardial hypertrophy by inhibiting AKT/eNOS signaling pathway.

关 键 词:压力超负荷心肌肥厚 内皮素转换酶-1 甲基化 AKT/eNOS信号通路 

分 类 号:R735.3[医药卫生—肿瘤]

 

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