Induction of early inflammatory gene expression in a murine model of nonresuscitated, fixed-volume hemorrhage.
Induction of early inflammatory gene expression in a murine model of nonresuscitated, fixed-volume hemorrhage.
复制标题
在非复苏、固定体积出血的小鼠模型中诱导早期炎症基因表达。
DOI：
10.1097/00024382-200204000-00015
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Vogel,StefanieN
中科院分区：
文献类型：
--
作者：
Rajnik,Michael;Salkowski,CindyA;Thomas,KarenE;Li,Ying-Yue;Rollwagen,FlorenceM;Vogel,StefanieN
许多与出血相关的终末器官问题的病因已被归因于对出血的炎症反应。在一个非复苏，固定量出血的小鼠模型中，我们试图阐明出血性损伤单独在早期炎症级联反应的产生中所起的作用。早在出血后1小时就可以发现差异，在研究的所有主要细胞因子基因中，3小时检测到一致的差异。与假手术组相比，在固定体积出血小鼠的肝脏和肺样本中均观察到IL-1β、IL-6、TNF-α和IL-10 mRNA表达显著上调。环氧合酶-2（考克斯-2）和诱导型一氧化氮合成酶（iNOS）基因在老龄小鼠的肝脏和肺中也上调。最后，出血增加了编码Toll样受体（TLR）-2和-4的基因的表达。总的来说，这些数据表明，与出血相关的初始炎症级联反应发生在初始出血事件后数小时内，并且可能与关键的促炎和抗炎细胞因子、酶和TLR基因的表达的显著调节相关，这表明这些可能是可能的新治疗靶点。
The etiology of many end-organ problems associated with hemorrhage has been attributed to the inflammatory response to hemorrhage. In a murine model of nonresuscitated, fixed-volume hemorrhage, we sought to elucidate the role that hemorrhagic insult alone plays in the generation of the early inflammatory cascade. Differences could be appreciated as early as 1 h post-hemorrhage, with consistent differences detected by 3 h in all of the major cytokine genes studied. Significant upregulation of IL-1β, IL-6, TNF-α, and IL-10 mRNA expression was observed in both the liver and lung samples of mice subjected to fixed-volume hemorrhage when compared with sham-hemorrhaged mice. The cyclooxygenase-2 (COX-2) and inducible nitric oxide synthetase (iNOS) genes also were upregulated in the livers and lungs of hemorrhaged mice. Finally, expression of the genes that encode the Toll-like receptors (TLR)-2 and-4 was increased by hemorrhage. Taken collectively, these data demonstrate that the initial inflammatory cascade associated with hemorrhage occurs within hours after the initial hemorrhagic event, and can be associated with significant modulation of expression of key pro-and anti-inflammatory cytokine, enzyme, and TLR genes, suggesting that these may be possible new therapeutic targets.