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目的探讨选择性腺苷A1受体(A1R)激动剂[R(-)-N6-(2-phenylisopropy1)adenosine(R-PIA)]在血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大反应中的作用及其机制,特别是与钙调神经磷酸酶(CaN)表达的关系。方法以体外培养的大鼠乳鼠心肌细胞为模型,应用AngⅡ(0.1μmol/L)诱导心肌细胞肥大,通过[3H]亮氨酸掺入法测定心肌细胞蛋白的生成速率;消化分离法及计算机图像分析系统检测心肌细胞体积。Western-blot蛋白印迹法测定心房钠肽(ANP)、CaN表达含量,观察选择性腺苷A1R激动剂R-PIA(1μmol/L)对心肌细胞肥大的抑制作用及机制。结果R-PIA(1μmol/L)可以明显抑制AngⅡ(0.1μmol/L)诱导的蛋白合成增加[R-PIA(976.2±89.0)vs AngⅡ(1130.7±102.7)计数/(min.孔),P<0.05],抑制细胞体积的增加[R-PIA(1448±145)vs AngⅡ(2306±163)μm3,P<0.05]和心肌细胞内ANP、CaN的表达含量增加。该抑制作用可以被A1R拮抗剂8-cyclopentyl-1,3-dipropylx-anthine(CPDPX)(0.1μmol/L)所拮抗。结论腺苷A1R激动剂R-PIA能抑制AngⅡ诱导的大鼠心肌细胞肥大,其作用主要是通过A1R介导。其机制可能与减少心肌细胞内CaN的表达有关。
Objective To investigate the role of selective adenosine A1 receptor (A1R) [R (-) - N6- (2-phenylisopropy1) adenosine (R-PIA)] in hypertrophic cardiomyocyte hypertrophy induced by angiotensin Ⅱ And its mechanisms, in particular its relationship with calcineurin (CaN) expression. Methods Cardiomyocytes were isolated from rat neonatal rat cardiomyocytes. Ang Ⅱ (0.1 μmol / L) was used to induce cardiomyocyte hypertrophy. Cardiomyocyte protein production was measured by [3H] leucine incorporation assay. Image analysis system detects cardiomyocyte volume. The inhibitory effect of selective adenosine A1R agonist R-PIA (1μmol / L) on cardiomyocyte hypertrophy and its mechanism were observed by Western blotting. Results R-PIA (1μmol / L) significantly inhibited the increase of protein synthesis induced by AngⅡ (9μmol / L) compared with that of AngⅡ (1130.7 ± 102.7) 0.05] and inhibited the increase of cell volume (R-PIA (1448 ± 145) vs AngⅡ (2306 ± 163) μm3, P <0.05] This inhibition can be antagonized by A1R antagonist 8-cyclopentyl-1,3-dipropylx-anthine (CPDPX) (0.1 μmol / L). Conclusion Adenosine A1R agonist R-PIA can inhibit Ang Ⅱ-induced rat cardiomyocyte hypertrophy, its role is mainly mediated by A1R. The mechanism may be related to reducing the expression of CaN in cardiomyocytes.