HO-1在AMPK抑制心肌肥大中作用.docVIP

HO-1在AMPK抑制心肌肥大中作用 　作者：陈广琴， 刘 晨， 张成喜， 蒙荣森， 陈保林， 熊肇军， 董吁 【摘要】 【目的】 研究AMP激活的蛋白激酶 (AMPK)及血红素氧合酶HO-1激活对心肌肥大的影响，以及HO-1在AMPK抑制心肌肥大中的作用。【方法】 以培养的新生大鼠心肌细胞为研究对象，采用蛋白免疫印迹杂交方法检测5-氨基-4甲酰胺咪唑核糖核苷酸(AICAR)对AMPK的磷酸化程度及对HO-1的影响，并测定心肌细胞 [3H]-亮氨酸掺入率及心肌细胞表面积，观察AMPK及HO-1心肌细胞肥大的影响。【结果】 AICAR对AMPK及HO-1均有激活作用，AICAR能阻断AngⅡ引起的心肌肥大效应;阻断HO-1的激活则能减弱AICAR的抑制作用。【结论】 AMPK具有抑制心肌肥大的作用，AMPK能激活HO-1，HO-1在AMPK抗心肌肥大的机制中起重要作用。 【关键词】 AMPK; HO-1; 心肌肥大 　　Abstract： 【Objective】 To investigate the effect of AMPK and HO-1 activation on hypertrophic cardiac myocyte， and the effect of HO-1 in the mechanism of AMPK inhibition of cardiomyocyte hypertrophy. 【Methods】 Cultured rat neonatal cardiacmyocytes were incubated with AngⅡ to induce cardiac hypertrophy. Cardiac myocyte surface area and [3H]leucine incorporation was measured to determine the effect of AMPK and HO-1 on cardiac hypertrophy. The effect of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on adenosine monophosphate activated protein kinase (AMPK) phosphorylation and HO-1 activaton were detected by Western blot. 【Results】 Compared with control group， activated AMPK significantly enhanced the transcriptive activity of AMPK， and increased HO-1 protein expression in cardiac myocyte. The increasement of cell surface area by Ang Ⅱ was significantly inhibited after treatment of AICAR. However， this inhibitory effect was attenuated by HO-1 inhibitor. 【Conclusion】 AMPK can attenuate the cardiac hypertrophy induced by Ang Ⅱ， AMPK can upregulate the HO-1 in cardiac hypertrophy induced by AngII. HO-1 play a significant role in the effect of the AMPK on inhibiting cardiac hypertrophy. 　　单磷酸腺苷激活的蛋白激酶(AMP-activated protein kinase，AMPK)是一种在真核细胞生物中广泛存在的丝氨酸/苏氨酸蛋白激酶，主要调节代谢和能量。AMPK由α，β和γ亚单位组成，其中α的α1和α2亚型主要分布于心肌[1-3]，心肌细胞中的AMPK的激活与心肌缺血、氧化应激及一些刺激因素如儿茶酚胺及血管紧张素有关[4-6]，最近有研究表明，AMPK能通过抑制心肌细胞蛋白质的合成减轻心肌细胞肥大[7]。HO-1是血红素氧合酶(HO)的同工酶之一，可被多种刺激因素如：缺血再灌注、热休克、重金属和低氧等诱导表达升高。HO-1作为一种新型的心肌保护因子，通过其产物的抗炎、抗氧化、抗凋亡和抗心律失常等作用在心血管疾病中发挥着重要的保护作用[8-11]，近年来一些研究结果显示，HO-1具有抑制心肌细胞肥大的作