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Downregulation of PI3K-gamma in a mouse model of sepsis-induced myocardial dysfunction

机译:脓毒症诱导的心肌功能障碍小鼠模型中PI3K-GAMMA的下调

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摘要

A key component during sepsis is the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, of which the PI3K-gamma isoform is a major regulator in many inflammatory responses. However, the role of PI3K-gamma in the development of sepsis-induced myocardial dysfunction (SIMD) is unknown. In this study, we established a model of SIMD induced by lipopolysaccharide (LPS), subsequently used the selective inhibitor LY294002 and AS605240 to block the effect of PI3K and PI3K-gamma, respectively. Cardiac function was evaluated by echocardiography, hearts were obtained for histological and protein expression examinations. ELISA was used to measure the serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), cardiac troponin I (cTnI) and heart-type fatty acid binding protein (H-FABP). LPS-treated mice showed an increase to cardiac inflammation, myocardial damage and production of TNF-alpha, IL-6, NF-kappa B, cTnI and H-FABP. Administration of AS605240 to LPS-treated mice reduced some patho-physiological characteristics of SIMD and reduced TNF-a, IL 6, cTnI and H-FABP production. However, administration of LY294002 did not improve those same conditions. The results showed that PI3K-gamma is likely a crucial element in SIMD by regulating the PI3K/Akt pathway, and become a new marker of myocardial injury. Inhibition of PI3K-gamma might be a potential therapeutic target in SIMD.
机译:在败血症期间的关键组分是磷酸阳性3-激酶(PI3K)/蛋白激酶激酶B(AKT)信号通路,其中PI3K-Gamma同种型是许多炎症反应中的主要调节剂。然而,PI3K-Gamma在败血症诱导的心肌功能障碍(SIMD)中的作用是未知的。在这项研究中,我们建立了由脂多糖(LPS)诱导的SIMD模型,随后使用选择性抑制剂LY294002和AS605240分别阻断PI3K和PI3K-γ的效果。心脏功能是通过超声心动图评估的,用于组织学和蛋白质表达检查的心脏。 ELISA用于测量肿瘤坏死因子α(TNF-α),白细胞介素-6(IL-6),心肌肌钙蛋白I(CTNI)和心型脂肪酸结合蛋白(H-FABP)的血清水平。 LPS治疗的小鼠表现出对心脏炎症,心肌损伤和TNF-α,IL-6,NF-Kappa B,CTNI和H-FAB的产生增加。施用AS605240至LPS处理的小鼠减少了SIMD的一些病例生理特性,降低了TNF-A,IL 6,CTNI和H-FABP生产。然而,Ly294002的给药没有改善相同的条件。结果表明,通过调节PI3K / AKT途径,PI3K-γ可能是SIMD中的关键因素,并成为心肌损伤的新标志物。对PI3K-γ的抑制可能是SIMD中的潜在治疗靶标。

著录项

  • 来源
    《Cytokine》 |2017年第2017期|共9页
  • 作者单位

    Chongqing Med Univ Affiliated Hosp 1 Dept Emergency Chongqing 400016 Peoples R China;

    Chongqing Med Univ Affiliated Hosp 1 Dept Emergency Chongqing 400016 Peoples R China;

    Hainan Med Coll Affiliated Hosp Dept Crit Care Med Hainan 571101 Peoples R China;

    Chongqing Med Univ Affiliated Hosp 1 Dept Emergency Chongqing 400016 Peoples R China;

    Chongqing Med Univ Affiliated Hosp 1 Dept Emergency Chongqing 400016 Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    Sepsis; Myocardial dysfunction; LPS; PI3K-gamma;

    机译:败血症;心肌功能障碍;LPS;PI3K-GAMMA;

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