The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment
The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment
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母体褪黑素治疗可恢复糖尿病妊娠成年后代受损的心肌缺血耐受性
DOI：
10.1111/jpi.12351
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发表时间：
2016-10-01
影响因子：
10.3
通讯作者：
Huang, He-Feng
中科院分区：
文献类型：
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作者：
Gao, Ling;Zhao, Yi-Chao;Huang, He-Feng
糖尿病妊娠的患病率越来越高，对胚胎发育有不利影响，并增加了成年后代血管代谢紊乱的风险。然而，对于母亲患糖尿病是否会增加后代成年后心脏损伤的易感性，人们仍然知之甚少。在这项研究中，我们观察到糖尿病小鼠和非糖尿病小鼠所生的成年后代的心脏功能和结构在基线上是相似的。然而，在心肌缺血/再灌注（MIR）的反应中，与对照组相比，糖尿病母亲后代表现出梗死面积增大、心功能障碍和心肌凋亡，这与线粒体和内质网（ER）应激介导的凋亡途径和氧化应激的过度激活有关。分子分析表明，糖尿病母系后代心肌缺血耐受性受损主要与心肌胰岛素受体底物（IRS）‐1/Akt信号通路钝化有关。此外，我们还研究了母体给药褪黑素对后代MIR应答的影响，结果表明妊娠期糖尿病母鼠接受褪黑素治疗可通过恢复心脏IRS‐1/Akt信号通路，显著改善后代对MIR损伤的耐受性。综上所述，这些数据表明，母亲糖尿病易使后代成年后MIR损伤增强，而在糖尿病妊娠期间补充褪黑素可能有助于改善后代的心肌缺血耐受性。
Diabetic pregnancy, with ever increasing prevalence, adversely affects embryogenesis and increases vasculometabolic disorder risks in adult offspring. However, it remains poorly understood whether maternal diabetes increases the offspring's susceptibility to heart injuries in adulthood. In this study, we observed that cardiac function and structure were comparable between adult offspring born to diabetic mice and their counterparts born to nondiabetic mice at baseline. However, in response to myocardial ischemia/reperfusion (MIR), diabetic mother offspring exhibited augmented infarct size, cardiac dysfunction, and myocardial apoptosis compared with control, in association with exaggerated activation of mitochondria‐ and endoplasmic reticulum (ER) stress‐mediated apoptosis pathways and oxidative stress. Molecular analysis showed that the impaired myocardial ischemic tolerance in diabetic mother offspring was mainly attributable to blunted cardiac insulin receptor substrate (IRS)‐1/Akt signaling. Furthermore, the effect of maternal melatonin administration on offspring's response to MIR was determined, and the results indicated that melatonin treatment in diabetic dams during pregnancy significantly improved the tolerance to MIR injury in their offspring, via restoring cardiac IRS‐1/Akt signaling. Taken together, these data suggest that maternal diabetes predisposes offspring to augmented MIR injury in adulthood, and maternal melatonin supplementation during diabetic pregnancy may hold promise for improving myocardial ischemic tolerance in the offspring.