【摘要】： 背景與目的:心肌肥大是心肌細(xì)胞受到各種肥大刺激因子作用后產(chǎn)生的一個復(fù)雜的病理生理過程,是機體為適應(yīng)過量負(fù)荷產(chǎn)生的一種適應(yīng)性、保護(hù)性措施。在這個過程中常常伴有心肌細(xì)胞體積增大、心肌纖維增生和胚胎基因的重新激活。由于心肌細(xì)胞出生之后不久即失去分裂增殖能力,所以這一過程并不伴有心肌細(xì)胞數(shù)目的增加。心肌肥大持續(xù)發(fā)展最終將導(dǎo)致心功能衰竭。 心肌營養(yǎng)素-1(Cardiotrophin-1,CT-1)是1995年,由Pennica在小鼠胚胎干細(xì)胞培養(yǎng)液中分離出來。由于它的化學(xué)結(jié)構(gòu)與白介素-6家族相似并且也可以與gp130受體結(jié)合,因此也被歸屬于白介素-6 (IL-6)及白血病抑制因子(LIF)細(xì)胞因子家族。研究發(fā)現(xiàn),它具有明顯的心肌細(xì)胞肥大刺激作用,是整個IL-6家族細(xì)胞因子中致心肌肥大作用最強的,此外它還具有促進(jìn)心肌細(xì)胞存活和抑制凋亡的作用。在體和離體的實驗發(fā)現(xiàn),CT-1可以引起心室腔直徑以及心肌細(xì)胞長度的增加。所以認(rèn)為CT-1介導(dǎo)的心肌肥大更傾向于容量超負(fù)荷的改變,而慢性容量超負(fù)荷最終將導(dǎo)致心肌不可逆性的功能喪失。但是這種容量負(fù)荷性心肌肥大并不同于壓力超負(fù)荷引起的心肌肥大,后者并沒見肌小節(jié)的增加,而是以心肌纖維的增生為主。實驗發(fā)現(xiàn),向心性肥大多是受到通過G蛋白偶聯(lián)受體通路以及ras信號通路作用的肥大刺激因子(如α/β腎上腺素能藥物、ET-1、AngⅡ、ISO等)的刺激。造成這兩大類肥大刺激因子作用后心肌形態(tài)差異的機理目前還不十分清楚,其中涉及到的受體、信號轉(zhuǎn)導(dǎo)也各不相同,機制十分復(fù)雜。 在整個心肌肥大過程中,存在著一類重要的轉(zhuǎn)錄調(diào)控因子——心肌轉(zhuǎn)錄因子,這其中又以GATA4最為重要。因為GATA4在整個轉(zhuǎn)錄因子
[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 偽 / 尾 adrenergic drugs, ET-1,Ang 鈪，

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