MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α
MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α
复制标题
MG53 通过上调过氧化物酶体增殖物激活受体-α 来预防脓毒症引起的心肌功能障碍
DOI：
10.1155/2020/7413693
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发表时间：
2020-08-27
影响因子：
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通讯作者：
Cao, Minghui
中科院分区：
文献类型：
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作者：
Han, Xue;Chen, Daili;Cao, Minghui
背景资料。心脏是败血症期间最常受到影响的器官之一。三明胶-53(Mitsugumin-53，MG53)因其心脏保护作用而引起了研究人员的关注。然而，MG53在脓毒症诱导的心肌功能障碍(SIMD)中的作用仍不清楚。本研究的目的是探讨MG53在SIMD中的作用机制，并探讨其与PPARα的关系。建立盲肠结扎穿孔(CLP)大鼠SIMD模型。于CLP后18h检测MG53和PPARα蛋白水平、心功能、心肌细胞损伤、心肌氧化应激和炎症指标以及心肌细胞凋亡。用重组人MG53(RhMG53)和PPARα拮抗剂GW6471进行预适应，观察MG53对SIMD中PPARα的影响。CLP后18h，心肌组织中MG53和PPARα的表达显著降低。与假手术组相比，CLP组大鼠心功能明显降低，与心肌破坏、氧化应激指标和促炎性细胞因子上调、心肌细胞过度凋亡有关。补充rhMG53可增强心肌MG53，在改善心功能的同时提高存活率，减少氧化应激、炎症和心肌细胞凋亡，这些与PPARα上调有关。GW6471可阻断MG53的上述保护作用。败血症休克后MG53和PPARα表达均下调。MG53补充剂通过上调PPARα的表达来保护心脏免受SIMD的影响。我们的研究结果为SIMD提供了一种新的治疗策略。
Background. The heart is one of the most commonly affected organs during sepsis. Mitsugumin-53 (MG53) has attracted attention in research due to its cardioprotective function. However, the role of MG53 in sepsis-induced myocardial dysfunction (SIMD) remains unknown. The purpose of this study was to explore the underlying mechanism of MG53 in SIMD and investigate its potential relationship with peroxisome proliferator-activated receptor-alpha (PPAR alpha).Methods. The cecal ligation and puncture (CLP) model was created to induce SIMD in rats. Protein levels of MG53 and PPAR alpha, cardiac function, cardiomyocyte injury, myocardial oxidative stress and inflammatory indicators, and cardiomyocyte apoptosis were measured at 18 h after CLP. The effects of MG53 on PPAR alpha in SIMD were investigated via preconditioning recombinant human MG53 (rhMG53) and PPAR alpha antagonist GW6471.Results. The expression of MG53 and PPAR alpha sharply decreased in the myocardium at 18 h after CLP. Compared with the sham group, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated oxidative stress indicators and proinflammatory cytokines, and excessive cardiomyocyte apoptosis in the CLP group. Supplementation with rhMG53 enhanced myocardial MG53, increased the survival rate with improved cardiac function, and reduced oxidative stress, inflammation, and myocardial apoptosis, which were associated with PPAR alpha upregulation. Pretreatment with GW6471 abolished the abovementioned protective effects induced by MG53.Conclusions. Both MG53 and PPAR alpha were downregulated after sepsis shock. MG53 supplement protects the heart against SIMD by upregulating PPAR alpha expression. Our results provide a new treatment strategy for SIMD.