急性给予脂联素对老年雌性大鼠心脏具有心脏保护作用。
Acute adiponectin delivery is cardioprotective in the aged female rat heart.
作者信息
Tomicek Nanette J, Hunter J Craig, Machikas Alexandra M, Lopez Veronica, Korzick Donna H
机构信息
Intercollege Program in Physiology, The Pennsylvania State University, University Park, Pennsylvania, USA.
出版信息
Geriatr Gerontol Int. 2015 May;15(5):636-46. doi: 10.1111/ggi.12306. Epub 2014 Aug 13.
AIM
The aged, post-menopausal female heart is characterized by reduced ischemic tolerance, and few therapies currently exist to limit ischemic damage. Adiponectin (APN), a cytokine produced in adipose tissue, limits infarct size and improves functional recovery after ischemia/reperfusion injury in adult hearts. The aim of the present study was to extend these previous studies and determine the cardioprotective efficacy of APN treatment in aged female rats.
METHODS
Hearts were isolated from adult (age 6-7 months; n = 10), aged (age 23 months; n = 14) and aged ovariectomized (n = 10) female rats, and subjected to ischemia/reperfusion injury. On ischemia, hearts were infused with 9 μg of APN or vehicle. Adiponectin receptor 1, adiponectin receptor 2 and adenosine monophosphate-dependent kinase (AMPK) were assessed by western blotting, tumor necrosis factor-α and nicotinamide adenine dinucleotide phosphate oxidase levels by real time polymerase chain reaction. Non-reducing western blotting for APN multimers in visceral adipose was also carried out.
RESULTS
APN infusion successfully improved post-ischemic left ventricular developed pressure (∼10-15%) and attenuated the rise in end diastolic pressure in all groups (P < 0.05). With ischemia/reperfusion injury, phospho-AMPK increased in all groups with additive effects of APN on increasing phospho-AMPK abundance in aged ovary-intact female rats only (P < 0.001). Age-associated increases in pre-ischemic tumor necrosis factor-α mRNA were unaffected by APN, whereas nicotinamide adenine dinucleotide phosphate oxidase 2 mRNA levels were attenuated by APN in adult and aged ovariectomized female rats. An age-associated decrease in cardiac adiponectin receptor 2 was observed in conjunction with elevated high molecular weight APN in adipose.
CONCLUSIONS
The present data suggest that APN might be a relevant therapy for protecting the aging female heart, albeit through divergent mechanisms that are likely influenced by age-associated estrogen availability.
目的
老年绝经后女性心脏的特点是缺血耐受性降低，目前几乎没有治疗方法可限制缺血损伤。脂联素（APN）是一种在脂肪组织中产生的细胞因子，可限制梗死面积并改善成年心脏缺血/再灌注损伤后的功能恢复。本研究的目的是扩展先前的这些研究，并确定APN治疗对老年雌性大鼠的心脏保护作用。
方法
从成年（6 - 7个月龄；n = 10）、老年（23个月龄；n = 14）和老年去卵巢（n = 10）雌性大鼠中分离心脏，并进行缺血/再灌注损伤。在缺血时，向心脏灌注9μg APN或载体。通过蛋白质印迹法评估脂联素受体1、脂联素受体2和腺苷酸活化蛋白激酶（AMPK），通过实时聚合酶链反应评估肿瘤坏死因子-α和烟酰胺腺嘌呤二核苷酸磷酸氧化酶水平。还对内脏脂肪中的APN多聚体进行了非还原蛋白质印迹分析。
结果
灌注APN成功改善了缺血后左心室舒张末压（约10 - 15%），并减轻了所有组舒张末期压力的升高（P < 0.05）。在缺血/再灌注损伤时，所有组的磷酸化AMPK均增加，APN仅对老年未去卵巢雌性大鼠的磷酸化AMPK丰度增加有叠加作用（P < 0.001）。缺血前肿瘤坏死因子-α mRNA与年龄相关的增加不受APN影响，而在成年和老年去卵巢雌性大鼠中，APN可降低烟酰胺腺嘌呤二核苷酸磷酸氧化酶2 mRNA水平。观察到心脏脂联素受体2与年龄相关的减少，同时脂肪中高分子量APN升高。
结论
目前的数据表明，APN可能是保护衰老雌性心脏的一种相关治疗方法，尽管其作用机制不同，可能受年龄相关的雌激素水平影响。
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