Anti-apoptotic, anti-fibrotic, and positive inotropic effects of ghrelin and GHRP on rat and mouse cardiac myocytes

ghrelin 和 GHRP 对大鼠和小鼠心肌细胞的抗凋亡、抗纤维化和正性肌力作用

• 批准号: nhmrc : 441113
• 负责人: Dr Morag Young
• 金额: $ 29.51万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/anti-apoptotic-anti-cardiac-myocytes/100352
• 关键词: Anti; apoptotic; anti; fibrotic; positive

Growth hormone (GH) is a protein hormone secreted from an endocrine organ, the pituitary gland, below the brain. Synthetic GH-releasing peptides (GHRPs) and endogenous GHRP (ghrelin) possess many other physiological functions in addition to the release of GH. GHRPs have been shown to affect cardiac function in animals and humans through their specific receptors. We recently demonstrated at single cell level that GHRPs increased contraction of cardiac muscle cells and protected them from the programmed cell death which occurs in heart failure and myocardial infarction. We also demonstrated that GHRPs protected the heart in chronic heart failure and alleviated functional loss of the heart in experimental heart failure models. Preliminary results now indicate that GHRPs prevent cardiac fibrosis, which accounts for cardiac dysfunction after heart failure and infarction. It is proposed in this project to clarify the mechanism underlying the action of GHRPs in (1) cardiac functional enhancing; (2) anti-cell death; (3) anti-fibrosis effects, in primary cultured rat myocytes in vitro and in cardiac diseased mouse models in vivo. By completing this project, we will be able to (1) better understand the physiological role of ghrelin in the regulation of cardiac function; and (2) clarify the potential for therapeutic use of GHRPs in the treatment of chronic heart failure, a disease affecting 1-2% of the population of Australia, with 5 year mortality rates about 65%.

生长激素（GH）是一种蛋白质激素，由大脑下方的内分泌器官脑垂体分泌。合成的生长激素释放肽（GHRPs）和内源性生长激素释放肽（ghrelin）除了释放生长激素外，还具有许多其他生理功能。GHRPs已被证明通过其特异性受体影响动物和人类的心脏功能。我们最近在单细胞水平证明GHRPs增加心肌细胞的收缩，并保护它们免受心力衰竭和心肌梗死中发生的程序性细胞死亡。我们还证明了GHRPs在慢性心力衰竭中保护心脏，并在实验性心力衰竭模型中减轻心脏功能丧失。现在的初步结果表明，GHRPs可以预防心脏纤维化，这是心力衰竭和梗死后心脏功能障碍的原因。本课题拟通过体外原代培养大鼠心肌细胞和体内心脏病小鼠模型，阐明GHRPs在（1）增强心脏功能;（2）抗细胞死亡;（3）抗纤维化等方面的作用机制。通过完成这个项目，我们将能够（1）更好地了解生长激素释放肽在调节心脏功能中的生理作用;（2）阐明GHRPs在治疗慢性心力衰竭中的治疗用途的潜力，慢性心力衰竭是一种影响澳大利亚1-2%人口的疾病，5年死亡率约为65%。