Intermedin is upregulated and has protective roles in a mouse ischemia/reperfusion model
Intermedin is upregulated and has protective roles in a mouse ischemia/reperfusion model
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Intermedin 上调并在小鼠缺血/再灌注模型中具有保护作用
DOI：
10.1038/hr.2009.120
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发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Huang, De-Jia
中科院分区：
文献类型：
--
作者：
Zhang, Heng-yu;Jiang, Wei;Huang, De-Jia
Intermedin （IMD）是一种新的降钙素/降钙素基因相关肽家族肽，具有血管舒张和正性肌力特性，在调节心血管稳态中具有多种功能，在心肌缺血/再灌注（MI/R）的病理生理中具有特别的意义。我们通过结扎左前降支建立小鼠心肌梗死/再灌注模型，探讨IMD及其受体复合物在心肌梗死/再灌注中的病理生理作用。与对照组相比，梗死小鼠血浆和心脏组织中IMD含量、mRNA和蛋白表达均升高。受体活性修饰蛋白3 （RAMP3）基因mRNA表达很早就升高，再灌注后降钙素受体样受体和RAMP2 mRNA水平升高。然而，RAMP1基因的表达没有改变。组织IMD含量与舒张压呈正相关，与脉压呈负相关。此外，外源性IMD治疗通过挽救脉压、抑制梗死周围中性粒细胞浸润、降低血浆肌酸激酶和乳酸脱氢酶活性，显著改善心肌梗死/R损伤。我们的研究结果表明，IMD在缺血心肌中上调，并可能诱导对心脏缺血损伤的重要有益细胞保护。高血压研究（2009）32,861-868；doi: 10.1038 / hr.2009.120;2009年8月14日在线发布
Intermedin (IMD), a new calcitonin/calcitonin gene-related peptide family peptide with vasodilatory and positive inotropic properties, has multiple functions in regulating cardiovascular homeostasis and is of particular interest in the pathophysiology of myocardial ischemia/reperfusion (MI/R). We created a mouse model of MI/R by ligating the cardiac left anterior descending artery to study the possible pathophysiological role of IMD and its receptor complexes in MI/R. Compared with the control, infarcted mice showed increased content, mRNA and protein expression of IMD in plasma and cardiac tissue. The mRNA expression of the receptor activity-modifying protein 3 (RAMP3) gene increased very early, and the calcitonin receptor-like receptor and RAMP2 mRNA levels increased later after reperfusion. However, the RAMP1 gene expression did not change. The tissue IMD content was positively correlated with the diastolic blood pressure and negatively correlated with pulse pressure. In addition, exogenous IMD treatment significantly ameliorated the MI/R injury by rescuing the pulse pressure, inhibiting neutrophil infiltration in the peri-infarction area, and decreasing the creatine kinase and lactate dehydrogenase activities in plasma. Our results indicated that IMD was upregulated in the ischemic myocardium and may induce important beneficial cytoprotection against cardiac ischemic injury. Hypertension Research (2009) 32, 861-868; doi: 10.1038/hr.2009.120; published online 14 August 2009