The Biological Effects And Mechanism Exploration Of Vaporized Perlfuorocarbon Inhalation On Primary Blast Lung Injury In Canines

Background and Objective: Primary blast lung injury (BLI) is a special type of acuterespiratory distress syndrome (ARDS). There is little treatment on BLI. In recent years,the treatment of perfluorocarbon (PFC) on ARDS is one of the hotest research areas.However, it has not been reported the effect of vaporized PFC on BLI. The aim of presentstudy was to investigate the effects of vaporized perfluorocarbon on BLI in canines’model and to discuss biological effects and potential mechanism.Methods: Thirty-six males or females crossbreed canines were divided randomly intofour groups: control group (C), BLI group（B), BLI+MV group (BM) and BLI+MV+PFCgroup (BMP). The venous blood and arterial blood were extracted every hour during theexperiment. The lung tissues were harvested at the end of the experiment and investigatedby histopathological and molecular biology techniques.①Small blast generator is usedto establish the BLI canines model.②The morphology of lung tissue, arterial blood gasindexes, respiratory mechanics and hemodynamics mechanics were investigatedrespectively; IL-6and TNF-α in plasma, bronchial alveolar lavage fluids (BALF) andlung tissue were detected by ELISA and real-time PCR respectively; MDA, SOD andGSH-PX in plasma, homogenization buffer of lung tissue were detected by colorimetricmethod respectively; Optical density of apoptosis positive cells in lung tissues weredetected by TUNEL. Bax, Bcl-2and actived Caspase-3in lung tissues were detected byreal-time PCR and western blot.③NF-κB, Nrf2and MAPK of four groups in lungtissues were detected by real-time PCR and western blot respectively.④Differentiallyexpressed miRNAs between B group and BMP group were detected by high-throughputstudy of miRNA chip. Results:1. In small blast generator induced BLI canines group, pulmonary edema,oxygenation declined, lung pathological changes aggravated. Vaporized PFC inhalationimproved gas exchange, airway resistance and had protective effects on the pathologicaldamages in the BLI canines’ model.2. After vaporized PFC inhalation, IL-6, TNF-αdecreased in the plasma, BALF and lung tissue. MDA decreased and SOD, GSH-PXincreased in the plasma and lung tissue. Apoptosis decreased and antiapoptosis increasedin Lung tissues. Airway resistance lower and lung static compliance improved in theBMP group compared to the BM group.3. The expressions of NF-κB, Nrf2and MAPKwere significantly increased respectively in BLI. After vaporized PFC inhalation,expressions of NF-κB decreased and Nrf2(Nucleus) increased, and the proteinexpressiongs of p-p38、p-JNK、p-ERK were significantly decreased respectively.4.23differentially expressed miRNA and449target genes between B group and BMP groupwere detected by high-throughput study of miRNA chip.Conclusion:1. It is an ideal BLI animal model induced by the small blast generator.2.Vaporized PFC inhalation could improve the pathological damage of the lung in the BLIcanines’ model.3. Vaporized PFC inhalation is involved in the change of relatedmolecules and pathways in BLI canines’ model.4. Differentially expressed miRNA showthat PFC may be playing a role on BLI.