Department of National Defense, Canadian Forces Health Services, Ottawa, ON Canada ; Critical Care Western, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON Canada ; Center for Critical Illness Research, Lawson Health Research Institute, 800 Commissioner's Rd E, N6A 5 W9 London, ON Canada.
Center for Critical Illness Research, Lawson Health Research Institute, 800 Commissioner's Rd E, N6A 5 W9 London, ON Canada.
J Inflamm (Lond). 2014 Oct 8;11(1):30. doi: 10.1186/s12950-014-0030-7. eCollection 2014.
Hemorrhagic shock and resuscitation (HS/R) can induce multiple organ failure which is associated with high mortality. The lung is an organ commonly affected by the HS/R. Acute lung injury is a major cause of dysfunction in other organ systems. The objective of this study is to test the hypothesis that HS/R causes increased gut permeability which results in induction of high mobility group box1 protein (HMGB1) and further leads to the development of acute lung inflammation.
A mouse model of HS/R was employed in this study. Gut permeability and bacterial translocation were assessed with circulating FD4 and lipopolysaccharide (LPS). Circulating HMGB1 was determined with ELISA. Acute lung inflammation (ALI) was determined with lung myeloperoxidase (MPO) activity and pulmonary protein leakage.
HS/R induced intestinal barrier dysfunction as evidenced by increased circulating FD4 and LPS at 30 min and 2 hrs after resuscitation, respectively. In addition, circulating HMGB1 levels were increased in mice with HS/R as compared with sham animals (p < 0.05). HS/R resulted in ALI (increased lung MPO activity and pulmonary protein leakage in mice with HS/R compared with sham mice, p < 0.05). Inhibition of HMGB1 (A-box and TLR4(-/-)) attenuated the ALI in mice with HS/R. However, inhibition of HMGB1 did not show protective effect on gut injury in early phase of HS/R in mice.
Our results suggest that induction of HMGB1 is important in hemorrhagic shock and resuscitation-induced acute lung inflammation.
失血性休克和复苏（HS/R）可导致多器官衰竭，与高死亡率相关。肺是常受 HS/R 影响的器官。急性肺损伤是其他器官系统功能障碍的主要原因。本研究的目的是检验以下假设，即 HS/R 导致肠道通透性增加，从而诱导高迁移率族蛋白 B1（HMGB1）的产生，并进一步导致急性肺炎症的发生。
本研究采用 HS/R 小鼠模型。通过循环 FD4 和脂多糖（LPS）评估肠道通透性和细菌易位。通过 ELISA 测定循环 HMGB1。通过肺髓过氧化物酶（MPO）活性和肺蛋白渗漏来确定急性肺炎症（ALI）。
HS/R 导致肠道屏障功能障碍，表现为复苏后 30 分钟和 2 小时时循环 FD4 和 LPS 分别增加。此外，与假手术动物相比，HS/R 小鼠的循环 HMGB1 水平升高（p<0.05）。与假手术小鼠相比，HS/R 小鼠发生 ALI（肺 MPO 活性和肺蛋白渗漏增加，p<0.05）。HMGB1 抑制（A 框和 TLR4(-/-)）减轻了 HS/R 小鼠的 ALI。然而，HMGB1 抑制在 HS/R 的早期阶段对肠道损伤没有保护作用。
我们的结果表明，HMGB1 的诱导在失血性休克和复苏诱导的急性肺炎症中很重要。
