Capturing the multifactorial nature of ARDS - "Two-hit" approach to model murine acute lung injury.
Capturing the multifactorial nature of ARDS - "Two-hit" approach to model murine acute lung injury.
复制标题
DOI：
10.14814/phy2.13648
复制
发表时间：
2018-03
影响因子：
2.5
通讯作者：
Vohwinkel CU
中科院分区：
文献类型：
--
作者：
Hoegl S;Burns N;Angulo M;Francis D;Osborne CM;Mills TW;Blackburn MR;Eltzschig HK;Vohwinkel CU
严重急性呼吸窘迫综合征（ARDS）通常表现为初始事件，随后需要机械通气。大多数ALI动物模型的局限性在于它们只关注急性肺损伤（ALI）的单一原因，因此无法模拟ARDS复杂的多因素病理学。为了更好地捕捉这种情况，我们提供了一个全面的表征模型的急性肺损伤结合两个损伤：气管内（i.t.）LPS或次氯酸（HCl）滴注，随后发生呼吸机诱导的肺损伤（VILI）。我们假设，与VILI相比，VILI之前用LPS或HCl预处理并因此接受（“两次打击损伤”）的小鼠将持续超累加性肺损伤。将小鼠分配至以下治疗组：对照组，i.t. NaCl，低吸气峰压（PIP）通气，i.t.盐酸，i.t. LPS、VILI（高PIP）、HCl i.t.然后是VILI和LPS i.t.其次是维力。以支气管肺泡灌洗液（BAL）中蛋白质含量、MPO活性、炎性细胞因子表达及组织病理学检查判断损伤程度。与单一肺损伤相比，在HCl或LPS滴注后经受VILI的小鼠显示增强的肺损伤。然而，接受i.t. VILI之前的LPS显示与经历i.t. HCl，然后是VILI。所描述的两次打击肺损伤模型，导致叠加性但差异性急性肺损伤，重新获得了临床相关的ALI多因素病因，可能是转化研究中有价值的工具。
Severe acute respiratory distress syndrome (ARDS) presents typically with an initializing event, followed by the need for mechanical ventilation. Most animal models of ALI are limited by the fact that they focus on a singular cause of acute lung injury (ALI) and therefore fail to mimic the complex, multifactorial pathobiology of ARDS. To better capture this scenario, we provide a comprehensive characterization of models of ALI combining two injuries: intra tracheal (i.t.) instillation of LPS or hypochloric acid (HCl) followed by ventilator‐induced lung injury (VILI). We hypothesized, that mice pretreated with LPS or HCl prior to VILI and thus receiving a (“two‐hit injury”) will sustain a superadditive lung injury when compared to VILI. Mice were allocated to following treatment groups: control with i.t. NaCl, ventilation with low peak inspiratory pressure (PIP), i.t. HCl, i.t. LPS, VILI (high PIP), HCl i.t. followed by VILI and LPS i.t. followed by VILI. Severity of injury was determined by protein content and MPO activity in bronchoalveolar lavage (BAL), the expression of inflammatory cytokines and histopathology. Mice subjected to VILI after HCl or LPS instillation displayed augmented lung injury, compared to singular lung injury. However, mice that received i.t. LPS prior to VILI showed significantly increased inflammatory lung injury compared to animals that underwent i.t. HCl followed by VILI. The two‐hit lung injury models described, resulting in additive but differential acute lung injury recaptures the clinical relevant multifactorial etiology of ALI and could be a valuable tool in translational research.