Treatment with D-β-hydroxybutyrate protects heart from ischemia/reperfusion injury in mice
Treatment with D-β-hydroxybutyrate protects heart from ischemia/reperfusion injury in mice
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DOI：
10.1016/j.ejphar.2018.04.019
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发表时间：
2018-06-15
影响因子：
5
通讯作者：
Zhao, Xianxian
中科院分区：
文献类型：
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作者：
Yu, Yongsheng;Yu, Yunhua;Zhao, Xianxian
本研究旨在观察D-5-羟基丁酸酯(BHB)对心脏缺血/再灌注(I/R)损伤的保护作用，并探讨其作用机制。雄性成年小鼠暴露于缺血30min和再灌流24 h。再灌流前5min皮下植入渗透泵，持续输注外源性BHb(1.6 mmol/kg/24 h)。补肾活血方治疗可减少心肌梗死面积，降低心肌肌钙蛋白I、肌酸激酶和乳酸脱氢酶水平，减轻心肌细胞凋亡，保护心功能。重要的是，补肾活血方对I/R小鼠的自噬通量有明显的促进作用，表现为心肌中Lc3-II/Lc3-I比值和p62蛋白表达降低，溶酶体相关膜蛋白-2(Lamp2)蛋白表达增强。补肾活血方治疗I/R小鼠后，可减少心肌线粒体内活性氧的生成，增加三磷酸腺苷的生成，减轻线粒体肿胀，并部分恢复心肌线粒体膜电位。此外，用BHB治疗I/R小鼠可减轻心肌氧化应激和内质网应激。结果表明，外源性BHB对小鼠心脏I/R损伤有保护作用。
The present study was designed to examine the protection of D-5-hydroxybutyrate (BHB) against ischemia/ reperfusion (I/R) injury in heart and investigate its underlying mechanism. Male adult mice were exposed to 30 min of ischemia and 24 h of reperfusion. Osmotic pumps were implanted subcutaneously 5 min before reperfusion for continuous delivery of the exogenous BHB (1.6 mmol/kg/24 h). Treatment with BHB reduced infarct size and levels of cardiac troponin I, creatine kinase and lactate dehydrogenase in serum, attenuated apoptosis in myocardium, and preserved cardiac function of I/R mice. Importantly, treatment of I/R mice with BHB promoted autophagic flux, evidenced by reduced the ratio of LC3-II/LC3-I and protein expression of p62 and enhanced protein expression of lysosome associated membrane protein-2 (Lamp2) in myocardium. Treatment of I/R mice with BHB reduced mitochondrial formation of reactive oxygen species, enhanced adenosine triphosphate production, attenuated mitochondrial swelling, and partly restored mitochondrial membrane potential in myocardium. Furthermore, treatment of I/R mice with BHB abated oxidative stress and attenuated endoplasmic reticulum stress in myocardium. Our results indicated that treatment with exogenous BHB protected heart from I/R injury in mice.