腺苷A1受体激动抑制高糖诱导的心肌细胞肥大

Activation of adenosine A_1 receptor inhibits glucose-induced cardiomyocyte hypertrophy

目的研究腺苷A1受体激动剂R(-)-N6-(2-phenyl-isopropyl)adenosine(R-PIA)对高糖(HG)诱导心肌细胞肥大的作用及机制。方法大鼠乳鼠心肌细胞培养,以HG(25.5mmol·L-1)诱导心肌细胞肥大模型,观察1μmol.L-1R-PIA和细胞外信号调节激酶1/2(ERK1/2)特异性抑制剂U0126对心肌肥厚的作用。用Lowry法测心肌细胞蛋白含量;Western blot法测心肌细胞p-ERK1/2的相对表达水平;Till图像测定系统测心肌细胞[Ca2+]i瞬间变化。结果1μmol·L-1R-PIA和U0126可以相似程度地抑制HG诱导的心肌细胞蛋白含量增加、p-ERK1/2相对表达增加及[Ca2+]i瞬间增加。合用0.1μmol·L-1腺苷Al受体拮抗剂8-eyelo-pentyl-1,3-dipropylxanthine(CPDPX)抑制作用消失。结论腺苷通过激动A1受体抑制HG诱导的心肌肥厚,其机制与减少心肌细胞p-ERK1/2的相对表达和降低[Ca2+]i瞬间变化有关。

Aim To demonstrate the effects and mechanism of adenosine A1 receptor agonist R（-）-N6-（2-phenylisopropyl） adenosine（R-PIA） on high glucose（HG）-induced myocardial hypertrophy by in vitro cultured myocardial cells from neonatal rats.Methods The protein content was assayed by the method of Lowry. The expression of p-ERK1/2 and ERK1/2 was determined by Western blot.The [Ca2^＋]i transient changes of cell loaded Fura-2/AM were measured by Till image system.Results 1 μmol·L^-1 R-PIA and U0126 inhibited similarly HG-induced increase of the protein content and [Ca2^＋]i transient along with the relative expression of p-ERK1/2.These responses were completely abolished by adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine（CPDPX）.Conclusion Adenosine A1 receptor stimulation significantly inhibits HG-induced myocardial hypertrophy by mediating ERK1/2 pathway and Ca^2＋.