Trehalose:: A biophysics approach to modulate the inflammatory response during endotoxic shock
Trehalose:: A biophysics approach to modulate the inflammatory response during endotoxic shock
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DOI：
10.1016/j.ejphar.2008.04.005
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发表时间：
2008-07-28
影响因子：
5
通讯作者：
Squadrito, Francesco
中科院分区：
文献类型：
--
作者：
Minutoli, Letteria;Altavilla, Domenica;Squadrito, Francesco
我们评估海藻糖对内源性休克的影响，在内源性休克中，生物膜完整性的丧失起着关键作用。此外，我们通过准弹性中子散射（QENS）研究进行了生物物理实验，以探讨海藻糖的膜稳定性效应是否与其关闭水扩散动力学的高能力相关，从而探讨相互作用的动力学机制。采用单次注射肠炎沙门氏菌脂多糖（LPS, 20 mg/kg/i.p）诱导雄性大鼠内毒素休克。LPS注射前30分钟和注射后2 h，随机给药（1 ml/kg/i.p）。0.9%NaCl)、蔗糖（1 g/kg/i.p）或海藻糖（1 g/kg/i.p）。测定肝和肺的平均动脉血压、核因子- κ B （nf - κ B）结合活性、κ B α和toll样受体-4 （TLR-4）活性。同时检测血浆肿瘤坏死因子- α (tnf - α)、白细胞介素-1 （IL-1）、白细胞介素-6 （IL-6）和丙二醛（MDA）。采用血丙氨酸转氨酶活性（ALT）研究肝损伤；诱导型一氧化氮合酶（iNOS）表达、髓过氧化物酶（MPO）活性和组织水肿评价。通过组织单核细胞趋化蛋白-1 （MCP-1）水平、MPO活性、iNOS表达和水肿形成等指标研究肺损伤。海藻糖降低低血压、nf - κ B结合活性、κ B α蛋白丢失和TLR-4激活。此外，海藻糖降低tnf - α、IL-1、IL-6和MDA水平。海藻糖还能钝化肝和肺损伤。QENS的测量还显示海藻糖具有很高的“关闭”能力。蔗糖不能改善内毒素休克引起的后遗症。海藻糖阻断内毒素休克引起的炎症级联反应，稳定生物膜，关闭水扩散动力学。(c) 2008 Elsevier B.V.版权所有
We evaluated the effects of trehalose against endotoxic shock, a condition in which the loss of bio-membrane integrity plays a pivotal role. In addition we performed a biophysics experiment by Quasi Elastic Neutron Scattering (QENS) study, to investigate whether the membrane stability effect of trehalose might be correlated with its high capability to switch-off the water diffusive dynamics and, hence, the kinetic mechanisms of interaction. Endotoxic shock was induced in male rats by a single injection of Salmonella enteritidis lipopolysaccharide (LPS; 20 mg/kg/i.p.). Thirty minutes before and 2 h after LPS injection, the animals were randomized to receive vehicle (1 ml/kg/i.p. 0.9%NaCl), sucrose (1 g/kg/i.p.) or trehalose (I g/kg/i.p.). Mean arterial blood pressure, Nuclear Factor-kappa B (NF-kappa B) binding activity, I kappa-B alpha and Toll-like receptor-4 (TLR-4) activation were evaluated in both liver and lung. Plasmatic tumor necrosis factor-alpha (TNF-alpha), Interleukin-1 (IL-1), Interleukin-6 (IL-6) and malondialdehyde (MDA) were also investigated. We studied liver injury by means of blood alanine aminotransferase activity (ALT); inducible nitric oxide synthase (iNOS) expression, myeloperoxidase (MPO) activity and tissue edema evaluation. Lung injury was investigated by means of tissue monocyte chemoattractant protein-1 (MCP-1) levels, MPO activity, iNOS expression and edema formation. Trehalose reduced hypotension, NF-kappa B binding activity, I kappa B alpha protein loss and TLR-4 activation. In addition trehalose reduced TNF-alpha, IL-1, IL-6 and MDA levels. Trehalose also blunted liver and lung injury. QENS measurements showed also that trehalose possesses a high "switching off" capability. Sucrose did not modify endotoxic shock-induced sequelae. Trehalose blocked the inflammatory cascade triggered by endotoxin shock, stabilizing the bio-membranes and switching off the water diffusive dynamics. (c) 2008 Elsevier B.V. All rights reserved.