Cellular interaction in pathogenesis of cardiac dysfuction

心衰是一种进行性疾病，预后较差，常伴有非自然心肌肥大。肥大或衰竭心脏中的基因表达改变已被确定为疾病进展的原因。另一方面，最近的证据表明心力衰竭的严重程度与血清肿瘤坏死因子α (tnf - α)浓度之间存在相关性，而tnf - α具有负性肌力作用。然而，tnf - α是否具有致病作用尚不清楚。在这项研究中，我们使用大鼠新生儿心肌细胞，在体外研究了tnf - α的作用。心肌细胞总蛋白浓度定量显示，FCS使单核细胞蛋白比无血清对照组增加了1.52倍，tnf - α浓度为1和10 ng/ml时也分别比对照组增加了1.24倍和1.18倍。与无血清对照组相比，添加1和10 ng/ml的tnf - α使心肌细胞培养中^ 3h标记的苯丙氨酸掺入量分别增加1.92倍和2.07倍。tnf - α浓度为1 ng/ml和10 ng/ml时，心房利钠肽基因转录增强率分别为对照的1.21和1.72倍，β -肌球蛋白重链基因转录增强率分别为对照的1.17和1.37倍。结果表明，thf - α在转录水平上促进心肌肥厚，强烈提示tnf - α加速心力衰竭的发病过程。

Heart failure is a progressive condition with poor prognosis, and it is accompanied by unnatural myocardial hypertrophy. Altered gene expression in the hypertrophied or failing heart has been identified as being responsible for the progression of the disease. On the other hand, recent evidence has indicated a correlation between the severity of heart failure and the serum concentration of tumor necrosis factor alpha (TNF-alpha), which has a negative inotropic effect. However, it is still unclear whether or not TNF-alpha has a pathogenic role. In this study, using cardiac myocytes from rat neonates, we studied the effects of TNF-alpha in vitro. Quanification of the total cardiac myocyte protein concentration revealed that FCS increased the monocyte protein by 1.52 times compared to that in the serum-free control, and TNF-alpha at the concentration of 1 and 10 ng/ml also increased the protein by 1.24 and 1.18 times, respectively, compared to the control value. The addition of TNF-alpha at 1 and 10 ng/ml increased the ^3H-labeled phenylalanine incorporation by 1.92 and 2.07 times in cardiac myocyte culture respectively, compared to that in the serum-free control. The enhancement of atrial natriuretic peptide gene transcription were 1.21 and 1.72 times control as 1 ng/ml and 10 ng/ml of TNF-alpha respectively, and those of beta-myosin heavy chain gene were 1.17 and 1.37 times control. As a result, it was concluded that THF-alpha promotes myocardial hypertrophy at the transcriptional level, strongly indicating that TNF-alpha accelerates the disease process of heart failure.