Delta opioid receptor agonist attenuates lipopolysaccharide-induced myocardial injury by regulating autophagy.
Delta opioid receptor agonist attenuates lipopolysaccharide-induced myocardial injury by regulating autophagy.
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DOI：
10.1016/j.bbrc.2017.06.029
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发表时间：
2017-10
影响因子：
3.1
通讯作者：
Pin Zhao;Jianke Kuai;Jinjian Gao;Li Sun;Yan Wang;Li-nong Yao
中科院分区：
文献类型：
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作者：
Pin Zhao;Jianke Kuai;Jinjian Gao;Li Sun;Yan Wang;Li-nong Yao
背景DADLE对脓毒症心肌损伤有保护作用。近年来，自噬被证实是脓毒症相关心肌损伤的一种先天性防御机制。然而，DADLE是否具有促自噬作用尚未阐明。本研究旨在探讨DADLE对脓毒症自噬的调节作用。LPS注射后，小鼠接受DADLE、纳曲吲哚或载体。ELISA法检测心肌肌钙蛋白I（cTnI）水平，JC-1法检测线粒体膜电位。心脏超微结构和自噬体通过透射电子显微镜观察。结果LPS腹腔注射后立即或4 h给予DADLE治疗，均能提高内毒素血症小鼠的存活率。DADLE可减轻LPS所致的心肌超微结构损伤，其心肌保护作用还可通过升高MMP水平、降低cTnI水平来体现。通过透射电镜和Western blot观察发现，DADLE处理后，自噬体数量和自噬相关蛋白LC 3 II、Beclin 1的表达明显增加。DADLE促进LPS诱导的自噬体成熟，如LAMP-1蛋白水平增加和SQSTM 1/p62蛋白水平降低所示。结论DADLE对LPS诱导的内毒素血症小鼠有明显的保护作用，并能提高内毒素血症小鼠的存活率。这种作用与自噬增加有关。
BackgroundPrevious studies have described the protective effects of DADLE on myocardial injury in sepsis. Recently, autophagy has been shown to be an innate defense mechanism in sepsis-related myocardial injury. However, whether DADLE has an pro-autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of DADLE on the regulation of autophagy during sepsis.MethodsMale mice were subjected to LPS or vehicle intraperitoneal injection. After LPS injection, mice received either DADLE, Naltrindole or vehicle. ELISA and JC-1 were used to evaluate the level cTnI and Mitochondrial membrane potential. Cardiac ultrastructural and autophagosomes were visualized by transmission electron microscopy. The relative protein levels were analyzed by Western blot.ResultsThe results showed that treatment with DADLE both immediately or 4 h after LPS intraperitoneal injection could improve the survival rate of mice with endotoxemic. DADLE could ease myocardium ultrastructure injury induced by LPS, this cardioprotective effect was also seen in increased MMP levels, and decreased cTnI levels. Through observation of transmission electron microscopy and Western blot we have discovered that the amount of autophagosome and the expression of autophagy related protein LC3II, Beclin1 were significantly increased with DADLE treatment. DADLE promoted LPS-induced autophagosome maturation as indicated by the increased LAMP-1 protein level and decreased SQSTM1/p62 protein level. The selective δ-opioid receptor antagonist Naltrindole play an opposite effects.ConclusionsDADLE could improve the survival and protect myocardial dysfunction in mice with LPS-induced endotoxemia. This effect was related to the increase of autophagy.