Procalcitonin as a predictive biomarker for total body irradiation-induced bacterial load and lethality in mice.
Procalcitonin as a predictive biomarker for total body irradiation-induced bacterial load and lethality in mice.
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DOI：
10.1097/shk.0b013e31825b2db3
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Hauer-Jensen M
中科院分区：
文献类型：
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作者：
Biju PG;Garg S;Wang W;Choudhry MA;Kovacs EJ;Fink LM;Hauer-Jensen M
脓毒症是重症监护病房死亡的主要原因。早期发现和干预对于预防死亡至关重要。急性放射综合征以胃肠道和造血系统损伤为特征。肠道菌群易位合并免疫系统受损可导致败血症和死亡。这项工作检查了降钙素原（一种临床败血症生物标志物）在辐射毒性小鼠模型中的效用。C57/BL6小鼠接受全身照射（TBI）。在体内测量肠粘膜通透性，并在基线和TBI后3.5、7和10天测量肝脏细菌负荷和血浆降钙素原（PCT）、脂多糖（LPS）和脂多糖结合蛋白（LBP）水平。通过受试者操作特征（ROC）分析确定早期PCT预测后续致死率的价值。TBI后4天，观察到肠粘膜通透性呈剂量依赖性增加，而从第7天开始，细菌易位存在。细菌易位与所有脓毒症生物标志物呈高度正相关，其中PCT相关性最强。此外，从第3.5天开始，血浆PCT水平已经升高，而LPS从第7天开始升高，LBP仅在TBI后10天升高。ROC分析显示，TBI后3.5天测量的PCT水平预测了10天的致死率。这些数据证明了PCT作为辐射诱导菌血症小鼠研究的早期生物标志物的价值，并表明其他败血症的临床结果可能适用于人类辐射后败血症。
Sepsis is the leading cause of mortality in intensive care units. Early detection and intervention are critical to prevent death. The acute radiation syndrome is characterized by damage of the gastrointestinal and hematopoietic systems. Translocation of intestinal microflora combined with immune system compromise may lead to septicemia and death. This work examined the utility of procalcitonin, a clinical sepsis biomarker, in a mouse model of radiation toxicity. C57/BL6 mice were exposed to total body irradiation (TBI). Intestinal mucosal permeability was measured in vivo, and liver bacterial load and plasma levels of procalcitonin (PCT), lipopolysaccharide (LPS), and lipopolysaccharide binding protein (LBP) were measured at baseline and 3.5, 7, and 10 days after TBI. The value of early PCT in predicting subsequent lethality was determined by receiver operator characteristics (ROC) analysis. Four days after TBI a dose-dependent increase in permeability of the intestinal mucosa was observed, while bacterial translocation was present from day 7 onward. There was a high positive correlation between bacterial translocation and all sepsis biomarkers, with PCT exhibiting the strongest correlation. Moreover, plasma PCT levels were elevated already from day 3.5 onwards, whereas, LPS was elevated from day 7 and LBP only 10 days after TBI. ROC analysis revealed that PCT levels measured 3.5 days after TBI predicted lethality at 10 days. These data demonstrate the value of PCT as an early biomarker in radiation-induced bacteremia for mouse studies and suggest that clinical results from other septic conditions may apply to post-radiation septicemia in humans.