心力衰竭发病机制中血管紧张素Ⅱ致肥大心肌细胞微管的变化

Alterations of microtubules in hypertrophied cardiomyocyte induced by angiotensin Ⅱin the pathogenesis of heart failure

目的:研究血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)致肥大心肌细胞微管的变化规律及骨架调控剂对肥大心肌细胞中微管重构的影响。方法:在Wistar大鼠乳鼠心肌细胞原代培养基础上,应用AngⅡ诱导建立肥大心肌细胞模型,采用免疫荧光法检测肥大心肌细胞中微管的空间重构及骨架调控剂对微管空间构象的影响。结果:AngⅡ组心肌细胞3H-亮氨酸掺入较对照组明显增强(P<0.05),提示蛋白质合成增强、细胞肥大。肥大心肌细胞中微管的荧光强度及密度增强,在AngⅡ作用的基础上,骨架调控剂秋水仙素及紫杉醇可致微管的密度分别减弱或增强。结论:AngⅡ可通过特定途径介导心肌细胞微管的重构,骨架调控剂秋水仙素及紫杉醇通过影响微管的聚合状态参与调控细胞对不同外来刺激的反应及细胞的跨膜信号转导。

AIM:To investigate the alterations of microtubules in hypertrophied cardiomyocytes induced by angiotensin Ⅱ(Ang Ⅱ) as well as the effects of colchicine and taxol on the reconstitution of microtubules. METHODS:The hypertrophied cardiomyocyte model was set up by Ang Ⅱbased on the primary culture of cardiomyocyte of infant Wistar rats. Model of hypertrophied cardiomyocytes was assessed by Leu incorporation. The structural reorganization of microtubules and the effect of colchicine and taxol on it were investigated with immunofluorescence. RESULTS: Leu incorporation in the Ang Ⅱgroup was significantly higher than that in the control group(P< 0.05), which indicated that the protein synthesis increased and cell hypertrophied. The fluorescence intensity and density of microtubules in hypertrophied cells increased, and on the basis of effect of Ang Ⅱ, the density of microtubules was decreased by colchicines while increased by taxol.Spacial conformation of microtubule can be rearranged in hypertrophied cardiomyocyte induced by Ang Ⅱ. Colchicine and taxol can bind with microtubule and change spacial conformation of microtubule thus has an effect on signal transduction in