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首页> 外文期刊>Intensive Care Medicine Experimental >Resuscitation fluid composition affects hepatic inflammation in a murine model of early sepsis
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Resuscitation fluid composition affects hepatic inflammation in a murine model of early sepsis

机译：复苏液成分会影响败血症早期小鼠模型中的肝脏炎症

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BackgroundFluid resuscitation is a crucial therapy for sepsis, and the use of balanced fluids and/or isotonic albumin may improve patient survival. We have previously demonstrated that resuscitation with normal saline results in increased hepatic leukocyte recruitment in a murine model of sepsis. Given that clinical formulations of albumin are in saline, our objectives were to develop a novel balanced electrolyte solution specifically for sepsis and to determine if supplementing this solution with albumin would improve the inflammatory response in sepsis. MethodsWe developed two novel buffered electrolyte solutions that contain different concentrations of acetate and gluconate, named Seplyte L and Seplyte H, and administered these solutions with or without 5% albumin. Normal saline with or without albumin and Ringer’s lactate served as controls. Sepsis was induced by cecal ligation and puncture (CLP), and the liver microvasculature was imaged in vivo at 6?h after CLP to quantify leukocyte recruitment. Hepatic cytokine expression and plasma cell-free DNA (cfDNA) concentrations were also measured. ResultsSeptic mice receiving either Seplyte fluid showed significant reductions in hepatic post-sinusoidal leukocyte rolling and adhesion compared to normal saline. Hepatic cytokine concentrations varied in response to different concentrations of acetate and gluconate in the novel resuscitation fluids but were unaffected by albumin. All Seplyte fluids significantly increased hepatic TNF-α levels at 6?h compared to control fluids. However, Seplyte H exhibited a similar cytokine profile to the control fluids for all other cytokines, whereas mice given Seplyte L had significantly elevated IL-6, IL-10, KC (CXCL1), and MCP-1 (CCL2). Plasma cfDNA was generally increased during sepsis, but resuscitation fluid composition did not significantly affect cfDNA concentrations. ConclusionsElectrolyte concentrations and buffer constituents of resuscitation fluids can modulate hepatic cytokine production and leukocyte recruitment in septic mice, while the effects of albumin are modest during early sepsis. Therefore, crystalloid fluid choice should be an important consideration for resuscitation in sepsis, and the effects of fluid composition on inflammation in other organ systems should be studied to better understand the physiological impact of this vital sepsis therapy.
机译：背景液体复苏是败血症的关键治疗方法，平衡液体和/或等渗白蛋白的使用可以改善患者的生存率。我们以前已经证明，在败血症的鼠模型中，用生理盐水进行复苏会导致肝白细胞募集增加。鉴于白蛋白的临床配方在盐水中，我们的目标是开发一种专门用于脓毒症的新型平衡电解质溶液，并确定是否向该溶液中补充白蛋白会改善脓毒症的炎症反应。方法我们开发了两种新型缓冲电解质溶液，分别含有不同浓度的乙酸盐和葡萄糖酸盐，分别命名为Seplyte L和Seplyte H，并在有或没有5％白蛋白的情况下使用这些溶液。含或不含白蛋白的生理盐水和林格氏乳酸作为对照。通过盲肠结扎和穿刺（CLP）诱发败血症，并在CLP后6？h对体内的微血管成像，以定量白细胞募集。还测量了肝细胞因子表达和血浆无细胞DNA（cfDNA）浓度。结果与生理盐水相比，接受任一种Seplyte液的败血症小鼠的肝窦窦后白细胞滚动和粘连均明显减少。肝细胞因子浓度响应于新型复苏液中乙酸盐和葡萄糖酸盐的不同浓度而变化，但不受白蛋白影响。与对照液相比，所有Seplyte液在6？h时均可显着增加肝TNF-α水平。但是，对于所有其他细胞因子，Seplyte H表现出与对照液相似的细胞因子谱，而给予Seplyte L的小鼠的IL-6，IL-10，KC（CXCL1）和MCP-1（CCL2）明显升高。败血症期间血浆cfDNA通常增加，但复苏液的组成并未显着影响cfDNA浓度。结论电解液的浓度和复苏液的缓冲液成分可以调节败血症小鼠的肝细胞因子产生和白细胞募集，而在败血症早期，白蛋白的作用适中。因此，选择晶体液应成为脓毒症复苏的重要考虑因素，应研究液体成分对其他器官系统炎症的影响，以更好地了解这种重要的脓毒症疗法的生理影响。

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