The Preventive Effect Of Inosine On The Decompression Sickness Induced By Fast Buoyancy Ascent Escape

Purpose:Due to the excessive exposure to high pressure so that the inert gas bubbles generate in situ,fast buoyant asent escape adopted in the rescue of submarine accident is accompanied by decompression sickness?DCS?.This study endeavored to investigate the preventive effect and relative mechanism of prophylactic inosine on the DCS in rats.Methods:1.Adult male Wistar rats were randomly divided into sham group,DCS control group,low dose inosine group,medium dose inosine group,high dose inosine group and clopidogrel group.Except the sham group,the rats were compressed to 1.6 MPa following an exponential curve of PT=P0?2T/7 and maintained the constant pressure for 242 s before being decompressed to 0.1 MPa at a rate of 3 m/s.In the low/medium/high dose inosine group,50/100/200 mg/kg inosine was given to the rats 30 minutes before the compression.Clopidogrel group was orally administrated of 50 mg/kg/day clopidogrel for 3 days before the hyperbaric exposure.The same volume of saline was delivered to the sham group and the DCS control group.After the decompression,rats were observed for the morbidity and mortality of DCS.Lung histologic analysis,wet/dry weight ratio,inflammatory factors?TNF-a,IL-6?,apoptotic factors?Bcl-2,Bax,caspase-3?and MAPK pathway proteins?ERK,p38,JNK?were measured at 0.5 h,12 h and 24 h after the decompression.2.According to preliminary results,the dosage regimen of 100 mg/kg inosine for preventing DCS is appropriate and detection at 0.5 h can find meaningful changes.To observe the effect of specific antagonists on the incidence of DCS,lung pathological damage,inflammatory response and apoptosis,A2 A receptor antagonist SCH52861,A₃ receptor antagonist MRS1523 and ERK signaling pathway inhibitor AZD6244 were respectively used before the administration of inosine.Results:1.Unsafe fast buoyant asent escape could cause the DCS with the morbidity of 95% and the mortality of 50%.Compared with the sham group,the pathological score,wet/dry weight ratio,TNF-?,IL-6 and cleaved caspase-3 of lung tissue were increased and the anti-apoptotic index Bcl-2/Bax was down-regulated in the DCS control group.2.Compared with the DCS control group,100²00 mg/kg inosine could effectively reduce the incidence of DCS and death of rats.The effect was similar to that of clopidogrel which has been proved to be effective for preventing DCS.Prophylactic inosine also reduced lung pathological score,wet/dry weight ratio,TNF-?,IL-6 and cleaved caspase-3 while up-regulating Bcl-2/Bax and phosphorylated ERK.This phenomenon was most obvious after 0.5 h out of the cabin.3.SCH52861,MRS1523 and AZD6244 prior to inosine pretreatment could deteriorate the DCS-related injury and eliminate the preventive effect of inosine.Conclusions:1.Unsafe fast buoyant ascent escape can lead to the DCS.The lung tissue shows significant pathological damage,edema,inflammatory response and increased levels of apoptosis within 12 h after decompression.2.100 mg/kg inosine pretreatment can effectively reduce the morbidity and mortality.Inosine plays a protective role in the early stage of DCS while improving the structural damage,inflammation and apoptosis of lung.3.By binding to A2 A and A3 receptors,inosine can activate ERK signaling pathway,down-regulate the inflammatory factors and apoptosis levels,relieve lung injury,and prevent the DCS caused by fast buoyant asent escape effectively.