心肌营养素-1对大鼠心肌转录因子GATA-4作用的实验研究

发布时间：2018-05-01 20:17

本文选题：心肌肥大 + 心肌营养素-1　；参考：《大连医科大学》2006年硕士论文

【摘要】： 目的:在长期心脏负荷过重时,心肌细胞对增加的机械应力和神经体液因子采取一系列的代偿适应性肥大反应,表现为心肌细胞的形态改变和特征性的基因表达变化。因此,对心肌细胞肥大的细胞和分子水平改变的充分了解是治疗心肌肥大及其随后发生的心力衰竭的迫切要求。研究表明,心肌转录因子,尤其是锌指结构转录因子GATA-4,因其支持着正常情况下及肥大反应后增加的各种结构蛋白和收缩蛋白的转录调节,而在多种肥大促进因素引起的心肌肥大反应中发挥着关键性作用。然而,GATA-4在一种新型的白细胞介素-6家族细胞因子成员——心肌营养素-1(Cardiotrophin-1, CT-1)引起心肌肥大过程中的作用尚未引起研究者的充分关注。CT-1是一种比目前已知的其他肥大激动剂更为强效的肥大促进因子,且CT-1所致的心肌肥大与G蛋白偶联受体激动剂引起的肥大表型有所不同,更类似于容量负荷过重条件下的离心性肥大,且更易于转变为不可逆的心功能损害及心衰。本实验的主要目的即为探讨CT-1是否对GATA-4的转录及DNA结合活性产生影响。方法:本实验研究了10-12mol/L、10-11mol/L、10-10mol/L、10-9mol/L或10-8mol/L CT-1作用10分钟、15分钟、30分钟、1小时、2小时、3小时、6小时、12小时、24小时或48小时后,对培养的新生大鼠心肌细胞内GATA-4基因转录和DNA结合活性的影响;观察了指示心肌肥大遗传表型改变的ANP mRNA表达水平变化和CT-1作用下心肌细胞的形态学改变;同时还记录了GATA-4的协同作用心肌转录因子Csx/Nkx2-5和MEF2C在CT-1刺激后的基因转录情况。结果:为验证实验过程的有效性,本实验首先观察了CT-1对ANP基因转录的影响。ANP mRNA表达在对照组里几乎检测不到。10-10mol/L CT-1刺激后3小时开始引起ANP基因转录增加,且其表达
[Abstract]:Aim: during long-term cardiac overload, cardiomyocytes responded to increased mechanical stress and neurohumoral factors by a series of compensatory adaptive hypertrophy responses, which were characterized by morphologic changes and characteristic gene expression changes in cardiomyocytes. Therefore, a full understanding of the cellular and molecular changes of cardiac hypertrophy is an urgent requirement for the treatment of cardiac hypertrophy and its subsequent heart failure. Studies have shown that myocardial transcription factors, especially zinc finger structural transcription factor GATA-4, support the transcriptional regulation of various structural and contractile proteins in normal and hypertrophic response. It plays a key role in cardiac hypertrophy response caused by various hypertrophic factors. However, the role of GATA-4 in cardiac hypertrophy induced by cardiotrophin-1 (CT-1), a novel cytokine member of the interleukin-6 family, has not yet attracted sufficient attention from researchers. CT-1 is a type of hypertrophy compared with other known hypertrophy. Agonists are more potent hypertrophy promoters, The hypertrophy induced by CT-1 is different from that induced by G protein coupled receptor agonists, which is more similar to centrifugal hypertrophy under excessive volume loading, and it is more likely to change to irreversible cardiac dysfunction and heart failure. The main purpose of this study was to investigate whether CT-1 affects the transcription and DNA binding activity of GATA-4. Methods: the effects of 10-12 mol / L 10-11 mol / L 10 -10 mol / L 10 -9 mol / L or 10-8mol/L CT-1 on GATA-4 gene transcription and DNA binding activity in cultured neonatal rat cardiomyocytes were studied after exposure to 10-12 mol / L 10 -10 mol / L or 10-8mol/L CT-1 for 10 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 24 hours or 48 hours, respectively. The changes of ANP mRNA expression and morphologic changes of cardiomyocytes induced by CT-1 were observed, and the gene transcription of Csx/Nkx2-5 and MEF2C induced by CT-1 were also recorded. Results: to verify the effectiveness of the experimental process, we first observed the effect of CT-1 on ANP gene transcription. ANP mRNA expression was hardly detected in the control group. 10-10 mol / L CT-1 stimulated the ANP gene transcription increased 3 hours later, and its expression began to increase.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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