Acute stress response in calorie-restricted rats to lipopolysaccharide-induced inflammation
Acute stress response in calorie-restricted rats to lipopolysaccharide-induced inflammation
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DOI：
10.1016/j.mad.2004.11.007
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发表时间：
2005-05-01
影响因子：
5.3
通讯作者：
Shimokawa, I
中科院分区：
文献类型：
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作者：
Tsuchiya, T;Higami, Y;Shimokawa, I
热量限制（CR）可能通过应激反应机制降低了许多生物体的发病率和死亡率。我们分析了CR大鼠对脂多糖（LPS）诱导的炎症刺激的急性期反应。6个月大的雄性F344大鼠，从6周龄开始随意喂食（AL）或30%卡路里限制饮食，静脉注射LPS，然后在0至8小时内处死。CR减轻了肝损伤，但未降低血浆中促炎细胞因子或一氧化氮（NO）的浓度。肝组织的Western blotting分析表明，CR不影响细胞质I-kappa B的降解和随后NF-kappa B的核易位，NF-kappa B是炎症攻击后的关键转录因子。我们还利用DNA阵列和聚类分析分析了0、1和4 h时肝脏基因表达谱。与AL组相比，CR在0 h上调了炎症介质及其相关分子的几个基因的表达，但在1和4 h时没有上调。CR在0 h下调了能量或外源代谢和应激反应蛋白的基因。在1 h时，CR相对下调的基因是蛋白酶和泛素-蛋白酶体途径的基因。目前的结果表明，CR在不抑制促炎反应的情况下减轻了肝损伤，保护作用来自于组成性表达的基因产物，而不是诱导性表达的基因产物。2004爱思唯尔爱尔兰有限公司所有航班预订。
Calorie restriction (CR) reduces morbidity and mortality in a wide range of organisms, possibly through the stress response machinery. We analyzed the acute phase response of CR rats to lipopolysaccharide (LPS)-induced inflammatory challenge. Six-month-old male F344 rats, fed ad libitum (AL) or a 30% calorie-restricted diet from 6 weeks of age, received an intravenous LPS injection and were then sacrificed between 0 and 8 h. CR attenuated liver injury without reduction in the plasma concentrations of proinflammatory cytokines or nitric oxide (NO). Western blotting analysis of liver tissue demonstrated that CR did not affect the degradation of cytoplasmic I-kappa B and subsequent nuclear translocation of NF-kappa B, a key transcription factor after inflammatory challenge. We also analyzed the liver gene expression profiles at 0, 1 and 4 h with DNA arrays and cluster analysis. Compared with the AL group, CR upregulated the expression of several genes for inflammatory mediators or their related molecules at 0 h, but not at 1 or 4 h. CR downregulated genes for energy or xenobiotic metabolism and stress response proteins at 0 h. At 1 h, the relatively downregulated genes by CR were those for proteases and the ubiquitin-proteasome pathway. The present results suggest that CR attenuates liver injury without suppression of the proinflammatory response, and that the protective effect emerges from constitutively, rather than inductively, expressed gene products. (c) 2004 Elsevier Ireland Ltd. All fights reserved.