CT-1致心肌细胞肥大的机制探讨及相关信号转导通路的研究
发布时间：2018-10-20 18:13
【摘要】： 背景与目的:心肌肥大是心肌细胞受到各种肥大刺激因子作用后产生的一个复杂的病理生理过程,是机体为适应过量负荷产生的一种适应性、保护性措施。在这个过程中常常伴有心肌细胞体积增大、心肌纤维增生和胚胎基因的重新激活。由于心肌细胞出生之后不久即失去分裂增殖能力,所以这一过程并不伴有心肌细胞数目的增加。心肌肥大持续发展最终将导致心功能衰竭。 心肌营养素-1(Cardiotrophin-1,CT-1)是1995年,由Pennica在小鼠胚胎干细胞培养液中分离出来。由于它的化学结构与白介素-6家族相似并且也可以与gp130受体结合,因此也被归属于白介素-6 (IL-6)及白血病抑制因子(LIF)细胞因子家族。研究发现,它具有明显的心肌细胞肥大刺激作用,是整个IL-6家族细胞因子中致心肌肥大作用最强的,此外它还具有促进心肌细胞存活和抑制凋亡的作用。在体和离体的实验发现,CT-1可以引起心室腔直径以及心肌细胞长度的增加。所以认为CT-1介导的心肌肥大更倾向于容量超负荷的改变,而慢性容量超负荷最终将导致心肌不可逆性的功能丧失。但是这种容量负荷性心肌肥大并不同于压力超负荷引起的心肌肥大,后者并没见肌小节的增加,而是以心肌纤维的增生为主。实验发现,向心性肥大多是受到通过G蛋白偶联受体通路以及ras信号通路作用的肥大刺激因子(如α/β肾上腺素能药物、ET-1、AngⅡ、ISO等)的刺激。造成这两大类肥大刺激因子作用后心肌形态差异的机理目前还不十分清楚,其中涉及到的受体、信号转导也各不相同,机制十分复杂。 在整个心肌肥大过程中,存在着一类重要的转录调控因子——心肌转录因子,这其中又以GATA4最为重要。因为GATA4在整个转录因子
[Abstract]:Background & objective: myocardial hypertrophy is a complex pathophysiological process of cardiomyocytes induced by various hypertrophic stimulators. It is an adaptive and protective measure to adapt to excessive load. This process is often accompanied by an increase in the size of myocardial cells, myocardial fiber proliferation and the reactivation of embryonic genes. Since cardiomyocytes lose their ability to divide and proliferate shortly after birth, this process is not accompanied by an increase in the number of cardiomyocytes. The sustained development of myocardial hypertrophy will eventually lead to heart failure. Myocardial nutrient 1 (Cardiotrophin-1,CT-1) was isolated from mouse embryonic stem cell culture medium by Pennica in 1995. Because its chemical structure is similar to that of interleukin-6 family and can bind to gp130 receptor, it is also belong to the family of interleukin-6 (IL-6) and leukemia inhibitor (LIF) cytokines. It is found that it has obvious stimulation of cardiomyocyte hypertrophy and is the strongest one of the cytokines of the whole IL-6 family. In addition, it can promote the survival of cardiomyocytes and inhibit apoptosis. In vivo and in vitro experiments, CT-1 can increase the diameter of ventricular cavity and the length of cardiac myocytes. It is suggested that CT-1 mediated myocardial hypertrophy is more prone to the change of volume overload, and chronic volume overload will eventually lead to irreversible loss of myocardial function. However, this volume-loaded myocardial hypertrophy is not the same as that caused by pressure overload, the latter does not show an increase in the muscle section, but mainly in the proliferation of myocardial fibers. It was found that concentric hypertrophy was mainly stimulated by hypertrophic stimulators (such as 伪 / 尾 adrenergic drugs, ET-1,Ang 鈪，
本文编号：2283989
[Abstract]:Background & objective: myocardial hypertrophy is a complex pathophysiological process of cardiomyocytes induced by various hypertrophic stimulators. It is an adaptive and protective measure to adapt to excessive load. This process is often accompanied by an increase in the size of myocardial cells, myocardial fiber proliferation and the reactivation of embryonic genes. Since cardiomyocytes lose their ability to divide and proliferate shortly after birth, this process is not accompanied by an increase in the number of cardiomyocytes. The sustained development of myocardial hypertrophy will eventually lead to heart failure. Myocardial nutrient 1 (Cardiotrophin-1,CT-1) was isolated from mouse embryonic stem cell culture medium by Pennica in 1995. Because its chemical structure is similar to that of interleukin-6 family and can bind to gp130 receptor, it is also belong to the family of interleukin-6 (IL-6) and leukemia inhibitor (LIF) cytokines. It is found that it has obvious stimulation of cardiomyocyte hypertrophy and is the strongest one of the cytokines of the whole IL-6 family. In addition, it can promote the survival of cardiomyocytes and inhibit apoptosis. In vivo and in vitro experiments, CT-1 can increase the diameter of ventricular cavity and the length of cardiac myocytes. It is suggested that CT-1 mediated myocardial hypertrophy is more prone to the change of volume overload, and chronic volume overload will eventually lead to irreversible loss of myocardial function. However, this volume-loaded myocardial hypertrophy is not the same as that caused by pressure overload, the latter does not show an increase in the muscle section, but mainly in the proliferation of myocardial fibers. It was found that concentric hypertrophy was mainly stimulated by hypertrophic stimulators (such as 伪 / 尾 adrenergic drugs, ET-1,Ang 鈪，
本文编号：2283989
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