The Research On The Mechanism And Chemoprophylaxis Of The Rat Lung Injury Caused By The Decompression Sickness Induced By Fast Buoyancy Ascent Escape

Fast buoyancy ascent escape is the general submarine escape manner adopted by themajority of naval forces all over the world. Along with the improvement of the submarinetechnical level and the variation of the modern war confront model, it is fast buoyancyascent escape from further depth that is the most urgent demand of naval submarine. Theprecondition of fast buoyancy ascent escape is the time-limit of hyperbaric exposure. Ifhyperbaric exposure time exceeds the time-limit, fast buoyancy ascent escape has the highrisk to result in the decompression sickness (DCS). The pathogenesis of DCS is that the airdissolved in the tissues and organs has exceeded the oversaturation safety coefficient, spillsin situ, forms air bubbles, blocks the blood circulation and damages the tissues and organs,induces the dysfunction of respiratory system, circulatory system and nervous system, evenresults in death. The lung is a significant damage target organ of DCS. Acute lunginjury(ALI) is currently defined as a phenomenon of acute diffuse lung inflammationwhose pathological characteristics is an acute onset of non-cardiogenic pulmonary edemaresulting from increased capillary-alveolar permeability[1]，and is a type of inflammatoryabnormality.Tumor necrosis factor alpha (TNF-α), interleukin1β and IL-6are the principalproinflammatory factors in the early phase of the inflammation. On the contrary, IL-10andIL-13are the major members of the anti-inflammatory factors. TNF-α and IL-1β not onlyactivate nuclear factor kappa B (NFκB) but are themselves induced by NFκB through apositive feedback mechanism to amplify inflammation[2]. However, the research on therole of these inflammatory factors in the pathological process of DCS (especially DCSinduced by fast buoyancy ascent escape) and ALI which is caused by DCS is scarce. Toapproach the pathomechanism of the lung tissue injury of DCS induced by fast buoyancyascent escape, we implemented the comparision study with the animal model of divingDCS through detecting the degree of lung injury,the lung messenger ribonucleic acid(mRNA) level and protein level variation of the inflammatory factors includingTNF-α,IL-1β,IL-6,IL-10,IL-13in our established rat animal model of the lung injury ofDCS induced by simulated fast buoyancy ascent escape; and studying the action ofTNF-α-NFκB signaling in the process of the lung injury of DCS induced by simulated fast buoyancy ascent escape to illustrate the relation between the pathological process and theabove inflammatory factors or NFκB signaling;and applying the pretreatment ofpyrrolidinedithiocarbamic acid (PDTC) or TNF-α antibody(Ab) to inhibit the nucleartranslocation of NFκB or neutralize the bioactivity of TNF-α so as to study the role of theTNF-α-NFκB signal pathway and the chemoprophylaxis of PDTC or TNF-αAb in theprocess of the rat lung injury of DCS induced by simulated fast buoyancy ascentescape(even DCS). In addition, we still studied the post-transcription regulation role ofmicroRNAs（miRs）in the pathological process.The experimental result displayed:First，the rat lung injury degree(lung pathology and Lung wet-to-dry weight ratio) wasmost severe at0.5hour(h) and12h within24h after DCS caused by simulated fastbuoyancy ascent escape; at the same time, the lung tissue protein levels of TNF-α, IL-1βand IL-6were also synchronously increased.Second, at0.5h after DCS caused by simulated fast buoyancy ascent escape, the ratlung tissue mRNA levels of TNF-α and IL-1β were higher than that of group diving DCS;and the rat lulng protein level of TNF-α increased significantly; on the contrary the rat lungprotein content of IL-13was reduced which was discordant with its mRNA level;especially the rat lung tissue mRNA change tendencies between group DCS caused bysimulated fast buoyancy ascent escape and group diving DCS were absolutely opposite.Third, the reverse transcriptase-quantitative polymerase chain reaction（RT-qPCR）results of miRs expression spectrum in rat lung tissue displayed, the discrepancy existedbetween group DCS caused by fast buoyancy ascent escape and group diving DCS.Compared with group air control, the rat lung tissue expression level of miR-181c wassignificantly reduced in group DCS caused by fast buoyancy ascent escape; and the ratlung tissue expression levels of miR-146a, miR-181a and miR-181b were significantlyincreased. Compared with group diving DCS, the rat lung tissue expression level of let-7ewas significantly increased in group DCS caused by fast buoyancy ascent escape; and therat lung tissue expression levels of miR-181b and miR-181c were also obviously reduced.Fourth, the pretreatment of PDTC and TNF-α Ab could ameliorate the rat survival rateand the degree of the rat lung tissue injury of DCS caused by fast buoyancy ascent escape,inhibit the rat lung tissue expression levels of the important inflammatory factors such asTNF-α,IL-1β and IL-6, especially reduce the rat lung content of TNF-α effectively, increase the rat lung tissue protein content of the inhibitor of nuclear factor κB (IκB) andreduce the rat lung tissue protein content of NFκB largely.Fifth, although TNF-α Ab could inhibit the rat lung tissue nuclear translocation ofNFκB of DCS caused by fast buoyancy ascent escape more effectively than PDTC, PDTCcould ameliorate the rat survival rate of DCS caused by fast buoyancy ascent escape moreeffectively than TNF-α Ab.The above experimental result indicated:First, the degree of the rat lung injury and the rat lung tissue expression variation ofthe inflammatory factors presented characteristic diphasic changes.Second, the reason of the rat lung injury at0.5h and12h after DCS caused bysimulated fast buoyancy ascent escape may be the serious imbalance of theproinflammatory factors and the anti-inflammatory factors.Third, the pathomechanism discrepancy of the lung injury between DCS caused bysimulated fast buoyancy ascent escape and diving DCS may be imperfectly same.Fourth, miR-181, miR-146a and let-7e may play the important roles of theposttranscription regulation in the pathological process of DCS caused by fast buoyancyascent escape and the ALI that it resulted in.Fifth, TNF-α-NFκB signal pathway is one of the important pathomechanisms of therat lung injury of DCS caused by fast buoyancy ascent escape(even DCS).Sixth, PDTC and TNF-α Ab have the important role of prevention to the rat lungtissue injury of DCS caused by fast buoyancy ascent escape.And the treatment protocolsof targeting TNF-α or/and NFκB are potential for the rat lung injury of DCS caused byfast buoyancy ascent escape (even DCS).