Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia
Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia
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DOI：
10.1371/journal.pone.0049159
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发表时间：
2012-11-08
期刊：
影响因子：
3.7
通讯作者：
Davidson, Nicholas O.
中科院分区：
文献类型：
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作者：
Dominguez, Jessica A.;Xie, Yan;Davidson, Nicholas O.
工作背景：小肠在脓毒症的病理生理学中起着至关重要的作用，并被称为全身炎症反应的“发动机”。一种提出的机制是肠源性毒性脂质因子在肠系膜淋巴中转运，诱导全身性损伤和远端器官衰竭。然而，所涉及的途径尚未被定义，肠乳糜微粒组装和分泌在运输这些脂质因子中的作用是未知的。在这里，我们研究了脓毒症的小鼠有条件的，精氨酸特异性删除微粒体甘油三酯转移蛋白（Mtp-IKO），表现出一个块在乳糜微粒组装连同脂质adsorbtion.Methodology/主要调查结果：Mtp-IKO小鼠和对照组进行intrichelheal注射与铜绿假单胞菌或无菌生理盐水。Mttp-IKO小鼠表现出降低的7天死亡率，与5/17（29%）的对照小鼠相比，0/20（0%）死亡（p
Background: The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor'' of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption.Methodology/Principal Findings: Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p