PPAR gamma activation protects the brain against microvascular dysfunction in sepsis
PPAR gamma activation protects the brain against microvascular dysfunction in sepsis
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DOI：
10.1016/j.mvr.2012.05.006
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发表时间：
2012-09-01
影响因子：
3.1
通讯作者：
Silva, A. R.
中科院分区：
文献类型：
--
作者：
Araujo, C. V.;Estato, V.;Silva, A. R.
脓毒症是一种严重的疾病，其特征是在感染的情况下发生全身炎症反应，并可能进展为多器官功能障碍和死亡。脑微循环的改变在严重脓毒症的发病机制中起着至关重要的作用，包括毛细血管密度的降低和白细胞沿毛细血管沿着运动的障碍。然而，脓毒症相关脑微循环改变的机制至今尚未明确。我们研究了过氧化物酶体增殖物激活受体γ（PPAR γ）选择性激动剂罗格列酮对脓毒症盲肠结扎穿孔（CLP）模型中脑中白细胞/内皮细胞相互作用和功能性毛细血管密度的影响。罗格列酮对脑微循环有明显的抗炎作用。在接受CLP并接受罗格列酮治疗的动物中，功能性毛细血管密度增加，白细胞滚动和粘附减少。我们的数据提供了证据，参与了过氧化物酶体增殖物激活受体γ激活白细胞内皮细胞的相互作用和毛细血管密度的改变。用罗格列酮治疗的动物的脑灌注改善，表明PPAR γ激活对脓毒症中的脑微血管功能障碍具有保护作用。(C)2012 Elsevier Inc. All rights reserved.
Sepsis is a severe disorder characterized by systemic inflammatory responses in the presence of an infection and may progress to multiple organ dysfunction and death. Alterations in cerebral microcirculation fulfill a crucial role in the pathogenesis of severe sepsis, and include a decrease in capillary density and disturbances in leukocyte movement along capillaries. Nevertheless, the mechanisms involved in sepsis-associated cerebral microcirculatory alterations have so far not been defined. We investigated the effect of the peroxisome proliferator-activated receptor gamma (PPAR gamma) selective agonist rosiglitazone on leukocyte/endothelial cell interaction and functional capillary density in the brain in the cecal ligation and puncture (CLP) model of sepsis. Anti-inflammatory effects of rosiglitazone on the cerebral microcirculation were marked. Functional capillary density increased and leukocyte rolling and adhesion were decreased in animals submitted to CLP and treated with rosiglitazone. Our data provide evidence for involvement of PPAR gamma activation in leukocyte-endothelium interactions and alterations in capillary density. Improved cerebral perfusion in animals treated with rosiglitazone, suggests that PPAR gamma activation is protective against cerebral microvascular dysfunction in sepsis. (C) 2012 Elsevier Inc. All rights reserved.