Shock waves increase pulmonary vascular leakage, inflammation, oxidative stress, and apoptosis in a mouse model

Abstract

Severe lung damage is a major cause of death in blast victims, but the mechanisms of pulmonary blast injury are not well understood. Therefore, it is important to study the injury mechanism of pulmonary blast injury. A model of lung injury induced by blast exposure was established by using a simulation blast device. The effectiveness and reproducibility of the device were investigated. Eighty mice were randomly divided into eight groups: control group and 3 h, 6 h, 12 h, 24 h, 48 h, 7 days and 14 days post blast. The explosive device induced an explosion injury model of a single lung injury in mice. The success rate of the model was as high as 90%, and the degree of lung injury was basically the same under the same pressure. Under the same conditions, the thickness of the aluminum film can be from 0.8 mm to 1.6 mm, and the peak pressure could be from 95.85 ± 15.61 PSI to 423.32 ± 11.64 PSI. There is no statistical difference in intragroup comparison. A follow-up lung injury experiment using an aluminum film thickness of 1.4 mm showed a pressure of 337.46 ± 18.30 PSI induced a mortality rate of approximately 23.2%. Compared with the control group (372 ± 23 times/min, 85.9 ± 9.4 mmHg, 4.34 ± 0.09), blast exposed mice had decreased heart rate (283 ± 21 times/min) and blood pressure (73.6 ± 3.6 mmHg), and increased lung wet/dry weight ratio(2.67 ± 0.11), marked edematous lung tissue, ruptured blood vessels, infiltrating inflammatory cells, increased NF-κB (4.13 ± 0.01), TNF-α (4.13 ± 0.01), IL-1β (2.43 ± 0.01) and IL-6 (4.65 ± 0.01) mRNA and protein, decreased IL-10(0.18 ± 0.02) mRNA and protein ( P < 0.05). The formation of ROS and the expression of MDA5 (4.46 ± 0.01) and IREα (3.43 ± 0.00) mRNA and protein were increased and the expression of SOD-1 (0.28 ± 0.02) mRNA and protein was decreased ( P < 0.05). Increased expression of Bax (3.54 ± 0.00) and caspase 3 (4.18 ± 0.01) mRNA and protein inhibited the expression of Bcl-2 (0.39 ± 0.02) mRNA and protein. The changes of pulmonary edema, inflammatory cell infiltration, and cell damage factor expression increased gradually with time, and reached the peak at 12-24 h after the outbreak, and returned to normal at 7-14 days. Detonation injury can lead to edema of lung tissue, pulmonary hemorrhage, rupture of pulmonary vessels, induction of early inflammatory responses accompanied by increased oxidative stress in lung tissue cells and increased apoptosis in mice experiencing blast injury. The above results are consistent with those reported in other literatures. It is showed that the mouse lung blast injury model is successfully modeled, and the device can be used for the study of pulmonary blast injury. Impact statement The number of patients with explosive injury has increased year by year, but there is no better treatment. However, the research on detonation injury is difficult to carry out. One of the factors is the difficulty in making the model of blast injury. The laboratory successfully developed and produced a simulation device of explosive knocking through a lar...

Quantitative proteomic analysis and identification of differentially expressed proteins involved in blast exposure-induced inflammatory response

“…The results of the present study demonstrated that blast exposure not only caused signi cant hemorrhage, edema, and in ammatory cell in ltration, but also greatly increased the expression of TNFα, IL-1β and TGFβ1, and reduced the expression of IL-10 in the lungs. It has been reported that blast exposure led to an early in ammatory response, accompanied by signi cant oxidative stress and apoptosis in lung tissue cells [28]. A similar study also found that blast exposure signi cantly increased the expression of systemic pro-in ammatory and anti-in ammatory cytokines, and signi cantly caused pulmonary edema, in ammation, endothelial damage, and bleeding.…”

“…Our previous studies found that blast injury caused a signi cant increased expression of interleukin-1 (IL-1β), IL-6 and tumor necrosis factor (TNF-α), a signi cant decreased expression of IL-10, an increase in Evans blue leakage, and an signi cant increase in in ammatory cell in ltration [14][15][16]. In addition, we have previously reported that blast exposure-induced in ammation in the lungs occurred within the rst 12-48 h and peaked at approximately 24 h [17]. Jason Smith et al [18] reported similar results that in ammation affected the lungs, which developed from 24 h to 48 h and peaked at about 48 h. However, current treatment plan for patients with lung blast injury mainly focuses on supportive care, intensive therapy and mechanical ventilation, and there is no speci c alternative therapy.…”

The protective effect of L-glutamine against acute Cantharidin-induced Cardiotoxicity in the mice

“…It suggested that cantharidin may inhibit PP2A activation by increasing SOD level. 2) In the general state, the tissue would increase the SOD and GSH level to protect cells from ROS damage in a short time, but ultimately reduced SOD and GSH level because of the continued consumption [ 29 , 30 ]. Considered that we took blood in an early time, it is possible.…”

Damage-Associated Molecular Patterns and Their Signaling Pathways in Primary Blast Lung Injury: New Research Progress and Future Directions

“…IL-1β, IL-6, and TNF-α are pro-inflammatory cytokines, while IL-10 is an anti-inflammatory cytokine. Tong et al [ 93 ] found that the mRNA and protein expression of IL-1 β, IL-6, and TNF-α increased, while the mRNA and protein expression of IL-10 decreased after PBLI, indicating the occurrence of inflammation. IL-1β, IL-6, IL-10, and TNF-α are extensively used as biomarkers to assess the degree of inflammatory response and are indicators of whether the treatment method has anti-inflammatory effects.…”