Adiponectin protects against myocardial ischaemia-reperfusion injury via AMP-activated protein kinase, Akt, and nitric oxide
Adiponectin protects against myocardial ischaemia-reperfusion injury via AMP-activated protein kinase, Akt, and nitric oxide
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DOI：
10.1093/cvr/cvn017
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发表时间：
2008-04-01
影响因子：
10.8
通讯作者：
Pernow, John
中科院分区：
文献类型：
--
作者：
Gonon, Adrian T.;Widegren, Ulrika;Pernow, John
目的低血浆脂联素水平与心血管疾病和2型糖尿病相关。本研究的目的是探讨是否脂联素在心肌缺血再灌注过程中发挥心脏保护作用，以及这种作用是否与一氧化氮（NO）的产生有关。方法和结果离体大鼠心脏进行30分钟的全球或局部缺血，然后再灌注60分钟。在缺血发作时，心脏接受载体、脂联素（3 μ g/mL）、NO合酶抑制剂硝基-L-精氨酸（L-NNA）（0.1 mM）或脂联素和L-NNA的组合。测定血流动力学、梗死面积、内皮型一氧化氮合酶（eNOS）、腺苷酸活化蛋白激酶（AMPK）和Akt的表达。与溶剂组相比，脂联素显著增加了再灌注期间的左心室功能和冠状动脉流量。L-NNA的共同管理废除了由脂联素诱导的心肌功能的改善。局部缺血再灌注后的梗死面积为溶剂组危险区域的40 +/- 6%。脂联素使梗死面积减少至19 ± 2%（P < 0.01）。L-NNA本身不影响梗死面积，但消除了脂联素的保护作用（梗死面积40 ± 5%）。结论脂联素通过激活AMPK和产生NO，减轻心肌缺血再灌注后收缩功能障碍，缩小心肌梗死范围。
Aims Cardiovascular disease and type 2 diabetes mellitus are associated with low plasma concentration of adiponectin. The aim of this study was to investigate whether adiponectin exerts cardioprotective effects during myocardial ischaemia-reperfusion and whether this effect is related to the production of nitric oxide (NO).Methods and results Isolated rat hearts were subjected to 30 min of either global or local ischaemia followed by 60 min of reperfusion. The hearts received vehicle, adiponectin (3 mu g/mL), the NO-synthase inhibitor nitro-L-arginine (L-NNA) (0.1 mM), or a combination of adiponectin and L-NNA at the onset of ischaemia. Haemodynamics, infarct size, and expression of endothelial NO-synthase (eNOS), AMP-activated protein kinase (AMPK), and Akt were determined. Adiponectin significantly increased left ventricular function and coronary flow during reperfusion in comparison with the vehicle group. Co-administration of L-NNA abrogated the improvement in myocardial function induced by adiponectin. Infarct size following local ischaemia-reperfusion was 40 +/- 6% of the area at risk in the vehicle group. Adiponectin reduced infarct size to 19 +/- 2% (P < 0.01). L-NNA did not affect infarct size per se but abolished the protective effect of adiponectin (infarct size 40 +/- 5%). Phosphorylation of eNOS Ser(177), AMPK Thr(172), and Akt Ser(473) was increased in the adiponectin group (P < 0.05).Conclusion Adiponectin protects from myocardial contractile dysfunction and limits infarct size following ischaemia and reperfusion by a mechanism involving activation of AMPK and production of NO.