BackgroundExposure to cold weather is associated with infaust cardiovascular responses, including myocardial infarction and arrhythmias. However, the exact mechanisms of these adverse changes in the myocardium under cold stress are unknown. This study was designed to investigate the mechanisms of cardiac injury induced by cold stress in mice.MethodsThe mice were randomly divided into three groups, normal control (no handling), 1-week cold stress and 2-week cold stress. We observed physiological changes of the mice and morphological changes of myocardium tissues, and we measured the changes of 3′-nitrotyrosine and 4-hydroxynonenal, the expression levels of superoxide dismutase-1, superoxide dismutase-2, Bax, Bad, Bcl-2, Nuclear factor erythroid-derived 2-like 2 (Nrf2) and Kelch like-ECH-associated protein 1 (Keap1) in myocardium by western blot. Besides, we detected mRNA of superoxide dismutase-1, superoxide dismutase-2, Bax, Bad, Bcl-2, Nrf2 and Keap1 by real-time PCR. One-way analysis of variance, followed by LSD-t test, was used to compare each variable for differences among the groups.ResultsEchocardiography analyses demonstrated left ventricle dysfunction in the groups receiving cold stress. Histological analyses witnessed inflammation, vacuolar and eosinophilic degeneration occurred in left ventricle tissues. Western blotting results showed increased 3′-nitrotyrosine and 4-hydroxynonenal and decreased antioxidant enzymes (superoxide dismutase-1 and superoxide dismutase-2) in the myocardium. Expression of Nrf2 and Keap1 followed a downward trend under cold exposure, as indicated by western blotting and real-time PCR. Expression of anti-apoptotic protein Bcl-2 also showed the same trend. In contrast, expression of pro-apoptotic proteins Bax and Bad followed an upward trend under cold exposure. The results of real-time PCR were consistent with those of western blotting.ConclusionsThese findings were very significant, showing that cold exposure induced cardiac injury by inhibiting the Nrf2-Keap1 signaling pathway.

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...

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ObjectiveTo investigate the protective effect of chitosan oligosaccharide (COS) on acute lung injury (ALI) caused by blast injury, and explore possible molecular mechanisms.MethodsA mouse model of blast injury-induced ALI was established using a self-made explosive device. Thirty mice were randomly assigned to control, ALI and ALI + COS groups. An eight-channel physiological monitor was used to determine the mouse physiological index. Enzyme linked immunosorbent assay was used to measure serum inflammatory factors. Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, immunofluorescence staining, real time-polymerase chain reaction and western blot assay were used to detect inflammatory reactions, oxidative stress and apoptosis.ResultsMice were sacrificed 24 hours after successful model induction. Compared with the ALI group, the heart rate, respiration and PCO2 were significantly lower, but the PO2, TCO2 and HCO3- were significantly higher in the ALI + COS group. Compared to ALI alone, COS treatment of ALI caused a significant decrease in the wet/dry lung weight ratio, indicating a reduction in lung edema, inflammatory cell infiltration, levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6 and nuclear factor kappa B mRNA and protein expression were reduced and IL-10 mRNA and protein expression was increased (P < 0.05). COS significantly inhibited reactive oxygen species, MDA5 and IREα mRNA and protein expressions, cell apoptosis and Bax and Caspase-3 mRNA and protein expressions, and significantly increased superoxide dismutase-1 mRNA expression, and Bcl-2 and Caspase-8 mRNA and protein expression (all P<0.05). COS significantly increased dimethylarginine dimethylaminohydrolase 1 (DDAH1) protein expression, and reduced ADMA and p38 protein expression (P< 0.05).ConclusionBlast injury causes inflammation, oxidative stress and apoptosis in the lung tissues of mice. COS has protective effects on blast injury-induced ALI, possibly by promoting DDAH1 expression and inhibiting ADMA and mitogen-activated protein kinase pathways.

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