Pimentel Rosangela Nascimento, Petroni Ricardo Costa, Barbeiro Hermes Vieira, Barbeiro Denise Frediani, Andrade Mariana Macedo, Ariga Suely Kumini, Soriano Francisco Garcia
1Laboratório de Investigação Médica - LIM 51, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil.
2Emergências Clínicas do Departamento de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo 455, room 3189, São Paulo, CEP 01246-903 Brazil.
J Inflamm (Lond). 2019 Jul 3;16:16. doi: 10.1186/s12950-019-0220-4. eCollection 2019.
Dysregulated inflammatory response is common cause of organ damage in critical care patients. Preconditioning/tolerance is a strategy to prevent exacerbated inflammation. The aim of this study is to analyze hypertonic saline 7.5% as a potential inducer of preconditioning that protect from a lethal dose of LPS and modulates systemic inflammatory profile in mice.
Male Balb/C mice received intravenous (i.v.) injections of Hypertonic solution (NaCl 7.5%) (0.8 ml) for 3 days, on day 8th was challenged with LPS 15 mg/kg. Controls with Saline 0.9%, urea and sorbitol were performed. Microarray of mRNA expression was analyzed from HS versus saline from macrophages to identified the pathways activated by HS.
HS preconditioning reduced mortality after LPS injection as well reduced the cytokines release in plasma of the animals challenged by LPS. In order to check how HS induces a preconditioning state we measured plasma cytokines after each HS infusion. Repeated HS injections induced a state of preconditioning that reprograms the inflammatory response, resulting in reduced inflammatory cytokine production. A microarray of mRNA demonstrated that Hypertonic solution increased the expression of several genes in special Mapkbp1 and Atf3.
hypertonic solution induces preconditioning/tolerance reducing mortality and inflammatory response after LPS challenge.
炎症反应失调是重症监护患者器官损伤的常见原因。预处理/耐受是一种预防炎症加剧的策略。本研究的目的是分析7.5%高渗盐水作为一种潜在的预处理诱导剂，它可保护小鼠免受致死剂量的脂多糖（LPS）影响，并调节全身炎症反应。
雄性Balb/C小鼠静脉注射（i.v.）高渗溶液（7.5%氯化钠）（0.8毫升），持续3天，在第8天用15毫克/千克的LPS进行攻击。设置0.9%生理盐水、尿素和山梨醇作为对照。分析高渗盐水组与生理盐水组巨噬细胞的mRNA表达微阵列，以确定高渗盐水激活的信号通路。
高渗盐水预处理降低了LPS注射后的死亡率，并减少了LPS攻击动物血浆中的细胞因子释放。为了检测高渗盐水如何诱导预处理状态，我们在每次注射高渗盐水后测量血浆细胞因子。重复注射高渗盐水可诱导一种预处理状态，该状态可重新编程炎症反应，从而减少炎症细胞因子的产生。mRNA微阵列显示，高渗溶液增加了几个基因的表达，特别是Mapkbp1和Atf3。
高渗溶液可诱导预处理/耐受，降低LPS攻击后的死亡率和炎症反应。
