Noninvasive Imaging of Stored Red Blood Cell-Transfusion Aggravating Sepsis-Induced Liver Injury Associated with Increased Activation of M1-Polarized Kupffer Cells.
Noninvasive Imaging of Stored Red Blood Cell-Transfusion Aggravating Sepsis-Induced Liver Injury Associated with Increased Activation of M1-Polarized Kupffer Cells.
复制标题
储存红细胞输注加重脓毒症引起的肝损伤的无创成像与 M1 极化库普弗细胞激活增加相关。
DOI：
10.1097/shk.0000000000000867
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发表时间：
2017-10
期刊：
影响因子：
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通讯作者：
Zhan LS
中科院分区：
文献类型：
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作者：
Wu T;Wang L;An J;Wu CY;Wang Y;Qian L;Zhou J;Zhang YL;Zhou QQ;Wang XH;Wang HF;Fu QX;Zhan LS
补充数字内容可在正文中获得，肝脏损伤对脓毒症的严重程度和结局有关键影响。储存的红细胞(RBCs)在脓毒症相关性肝损伤发病机制中的作用尚不清楚。因此，为了研究储存红细胞输注对脓毒症所致肝损伤的影响及其相关机制，我们构建了一种脓毒症小鼠模型，该模型能够对常见的革兰氏阴性呼吸道病原体铜绿假单胞菌引起的细菌感染进行无创性成像。我们发现，体内输注储存的红细胞可增强脓毒症引起的肝损伤，肝脏损伤加重了脓毒症的严重程度，并降低了铜绿假单胞菌感染小鼠的存活率。储存红细胞输注可促进促炎细胞因子如肿瘤坏死因子α、白介素6和白介素1β的产生，这些细胞因子在铜绿假单胞菌感染的小鼠脓毒症相关性肝损伤中起重要作用。进一步的研究表明，观察到的炎症增强与M1极化的库普弗细胞的激活增加有关，该细胞产生许多炎症细胞因子，包括肿瘤坏死因子-α和IL-6。此外，M1极化的Kupffer细胞和分泌的促炎细胞因子通过增强Jun氨基末端激酶的激活和抑制核因子-kappaB的激活而对肝细胞发挥作用，表明与储存的红细胞一起输注破坏了肝脏细胞存活和细胞死亡之间的平衡。了解储存的红细胞可能导致这些并发症的机制可能有助于为使输血更安全提供指导。
Supplemental Digital Content is available in the text Liver injury has a critical effect on the severity and outcome of sepsis. The impact of stored red blood cells (RBCs) on the pathogenesis of sepsis-associated hepatic injury is not well understood. Therefore, to investigate the effects of stored-RBC transfusion on sepsis-induced liver damage as well as the associated mechanism, we constructed a sepsis mouse model enabling noninvasive imaging of bacterial infection caused by Pseudomonas aeruginosa, a common gram-negative respiratory pathogen. We showed that transfusions with stored RBCs enhanced sepsis-induced liver injury in vivo, and liver injury exacerbated the severity of sepsis and decreased survival in P aeruginosa-infected mice. Stored-RBC transfusions enhanced the production of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), and IL-1β, which play important roles in sepsis-associated liver injury in P aeruginosa-infected mice. Further study showed that the enhanced inflammation observed was associated with increased activation of M1-polarized Kupffer cells, which produce many inflammatory cytokines, including TNF-α and IL-6. Moreover, the M1-polarized Kupffer cells and secreted proinflammatory cytokines exerted their effects on hepatocytes through enhanced Jun N-terminal kinase activation and inhibited nuclear factor-kappaB activation, demonstrating that transfusion with stored RBCs disrupted the balance between cell survival and cell death in the liver. Understanding the mechanisms whereby stored RBCs might contribute to these complications will likely be helpful in providing guidance toward making transfusions safer.