摘要
目的在原代培养的新生大鼠心肌细胞的基础上,观察丹参酮ⅡA磺酸钠盐(STS)对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大的影响,以探讨STS在钙调神经磷酸酶(CaN)依赖的信号通路心肌肥大中的作用。方法以培养的原代心肌细胞为模型,用AngⅡ刺激细胞外Ca2+内流,丹参酮ⅡA及钙离子拮抗剂维拉帕米(Ver)进行干预,检测心肌细胞[Ca2+]i及钙调神经磷酸酶(CaN)、丝裂素活化蛋白激酶(MAPK)和蛋白激酶C(PKC)活性;[3H]-亮氨酸掺入法测定心肌细胞蛋白质合成速率作为心肌细胞肥大的指标。结果AngⅡ剌激组[Ca2+]i水平及蛋白核酸合成速率明显增高,与对照组相比差异显著(P<0·01),而STS能有效地降低由AngⅡ剌激引起的[Ca2+]i增高(P<0·01vsAngⅡ组),明显抑制AngⅡ诱导的蛋白质合成速率的增加(P<0·01vsAngⅡ组)。AngⅡ刺激组CaN、PKC活性与对照组相比差异有显著性(P<0·05、P<0·01)。STS及Ver抑制AngⅡ介导的心肌细胞CaN、PKC活性的增高。结论CaN通路在AngⅡ刺激的心肌细胞肥大中起重要作用;STS具有Ca2+阻滞剂的特点,能有效地降低由AngⅡ剌激引起的[Ca2+]i增高,导致CaN活性降低阻滞心肌肥大的发生和发展。
Objective To study the role of calcineurin （CaN）-dependent signaling pathway in cardiomyocytes hypertrophy and the effect of sodium tanshinone Ⅱ A sulfonate （STS） on the hypertrophy induced by angiotensin Ⅱ（Ang Ⅱ ）in the culture cardiomyocytes. Methods Myocytes [Ca^2＋]i was determined using fura-2 labelled method by fluroscence microscope. Mitogen activated protein kinase （ MAPK） and protein kinase C（PKC） and CaN activities was measured. Protein synthesis rate was measured by [^3H]-Leucine incorporation as the index of cardiomyocyte hypertrophy. Results Synthesis rate of protein and intracellular Ca^2＋ level stimulated by Ang Ⅱ in the cardiomyocytes was increased significantly （ P〈 0. 01） ; STS effectively decrease the increased intracellular Ca^2＋ level induced by Ang Ⅱ （P〈0.01 vs Ang Ⅱ group）and markedly inhibited the syntheses of protein （P〈0. 01 vs Ang Ⅱ group）. STS and vera pamil（ Ver） also suppressed the activities of the cardiomyocytes CaN and PKC stimulated by Ang Ⅱ in the cardiomyocytes. Conclusion STS effectively decrease the increased intracellular Ca^2＋ level induced by Ang Ⅱ and inhibite the activities of the CaN and PKC in cardiomyocytes.
出处
《高血压杂志》
CAS
CSCD
北大核心
2005年第8期488-491,共4页
Chinese Journal of Hypertension
基金
湖北省自然科学基金(2000J064)。
