DHEA-dependent and organ-specific regulation of TNF-alpha mRNA expression in a murine polymicrobial sepsis and trauma model.
DHEA-dependent and organ-specific regulation of TNF-alpha mRNA expression in a murine polymicrobial sepsis and trauma model.
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DOI：
10.1186/cc7963
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
van Griensven M
中科院分区：
文献类型：
--
作者：
Barkhausen T;Hildebrand F;Krettek C;van Griensven M
脱氢表雄酮(DHEA)可改善创伤和败血症后的存活率，但其作用机制尚不完全清楚。因此，我们在二次打击模型中研究了DHEA对局部细胞因子表达的影响。雄性NMRI小鼠造成股骨骨折/失血性休克和随后的脓毒症。以假手术组动物为对照。每日给予脱氢表雄酮(25 mg/kg)或赋形剂。脓毒症诱导后每天测定死亡率、活动度和体温。观察48h和96h肺、肝组织中肿瘤坏死因子-α、白介素1β和白介素10mRNA的表达模式。脱氢表雄酮治疗可显著降低死亡率和改善临床状况。在细胞因子水平上，盲肠结扎穿刺剂组48h后仅肿瘤坏死因子-α在两种组织中显著降低。这种抑制可以通过DHEA管理来恢复。相比之下，96小时后，在CLP-Vehicle组中，肿瘤坏死因子-α表达上调，而在肝组织中，去氢表雄酮治疗后仍保持中等水平。脱氢表雄酮治疗和创伤后的改善结果与48小时后肝和肺中肿瘤坏死因子-α的恢复以及96小时后肝脏中肿瘤坏死因子-α的逆调节减弱相一致。因此，脱氢表雄酮似乎是一种有效的肿瘤坏死因子α表达调节剂，具有时间和器官依赖性。
Dehydroepiandrosterone (DHEA) improves survival after trauma and sepsis, while mechanisms of action are not yet fully understood. Therefore, we investigated the influence of DHEA on local cytokine expression in a two-hit model. Male NMRI mice were subjected to femur fracture/hemorrhagic shock and subsequent sepsis. Sham-operated animals were used as controls. DHEA (25 mg/kg) or vehicle was administered daily. Mortality rate, activity and body temperature were determined daily after sepsis induction. TNF-α, IL-1β and IL-10 mRNA expression pattern were investigated in lung and liver tissue after 48 and 96 hours. DHEA treatment resulted in a significantly reduced mortality rate and improvements in the clinical status. On cytokine level, only TNF-α was significantly reduced in the cecal ligation and puncture (CLP)-vehicle group in both tissues after 48 hours. This suppression could be restored by DHEA administration. In contrast, after 96 hours, TNF-α was up-regulated in the CLP-vehicle group while remaining moderate by DHEA treatment in liver tissue. The improved outcome after DHEA treatment and trauma is coherent with restoration of TNF-α in liver and lung after 48 hours and a counter-regulatory attenuation of TNF-α in liver after 96 hours. Thus, DHEA seems to act, time and organ dependent, as a potent modulator of TNF-α expression.
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影响因子：
6.4
作者：
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