| Decompression sickness(DCS)refers to a series of symptoms such as skin,muscle,and joints caused by the formation of bubbles in blood vessels or tissues caused by dissolved inert gases during a period of excessive speed or amplitude of environmental pressure reduction.In severe cases,it can cause respiratory and circulatory dysfunction and lead to death.DCS is a common occupational disease among divers,and it can also occur during the underwater escape of submarine troops.Fast buoyancy ascent escape is the main submarine escape technology used by military powers around the world,with characteristics of speed,safety,and stability.However,once an accident occurs during the escape process,and the escape personnel are exposed to a high-pressure environment that exceeds the safety time limit,serious DCS may occur.Compared to conventional DCS,fast buoyancy ascent escape is mainly caused by exposure of the body to higher pressure and shorter exposure time.The bubbles generated during decompression mainly come from tissues such as venous blood,lungs,and heart.Therefore,the target organs damaged by DCS are mainly the respiratory system and circulatory system.However,due to the complexity of DCS pathogenesis and the severity of DCS caused by fast buoyancy ascent escape,there is currently no ideal drugs for DCS caused by fast buoyancy ascent escape.Therefore,searching for new drugs is the key to the treatment of DCS caused by fast buoyancy ascent escape.Nicotiflorin,an active monomer derived from the traditional Chinese medicine Carthami Flos for promoting blood circulation and resolving stasis,is a new class I traditional Chinese medicine for the treatment of acute ischemic stroke.Currently,Phase I clinical trials have been completed.Nicotiflorin has a variety of pharmacological effects such as antiplatelet aggregation,anti-inflammatory,antioxidant,antithrombotic,neuroprotective,and vascular endothelial cell protection,providing an important basis for protecting against inflammatory damage,platelet activation,aggregation,and vascular endothelial damage caused by DCS after fast buoyancy ascent escape.Based on the needs of diving and military medicine,this study applied an experimental rat model simulating fast buoyancy ascent escape leading to DCS to comprehensively evaluate the protective effect of nicotiflorin on DCS after preventive administration,and explore the target organs of nicotiflorin protective effect on DCS and its protective mechanism against DCS induced acute lung injury.We also explored the sustained protective effect of nicotiflorin administered after the occurrence of DCS on acute lung injury in experimental rats within 24 hours.Specifically,it can be divided into four parts.1.The effect of Nicotiflorin preventive administration on the severe incidence rate,survival rate and behavior of DCS rats caused by fast buoyancy ascent escape.According to the results of the pre-experiment,male SD rats were divided into seven pre-treatment groups: normal pressure control;DCS;low and high(100mg/kg,200mg/kg)doses of inosine;low,medium,and high(5mg/kg,10mg/kg,20mg/kg)doses of nicotiflorin.Rats in each group were injected 30 minutes before the start of the experiment.DCS modeling of experimental animals using 1.5 MPa exposure for242 s to simulate fast buoyancy ascent escape.Within 30 minutes after the end of escape,observe and record the symptoms of movement disorders,limb paralysis,convulsions,and death in experimental rats,determine the incidence of severe DCS in experimental rats,and score the behavioral status of experimental rats.The results showed that nicotiflorin could reduce the behavioral score of DCS rats in a dose-dependent manner(P<0.001),reduce the incidence rate of severe DCS from63.3% to 12.5%(P<0.001),reduce the mortality from 60.0% to 12.5%(P<0.001),delay the occurrence time of severe DCS(P<0.001),and prolong the survival time of rats(P<0.001).The above results suggest that nicotiflorin has a good protective effect on DCS caused by simulated fast buoyancy ascent escape.2.The effect of Nicotiflorin preventive administration on Lung,Brain,and Liver Tissue of DCS Rats Induced by fast buoyancy ascent escapeThe measurement results of wet/dry weight ratio of lung tissue and the histopathological observation results of HE staining in lung,brain,and liver tissues of rats in each pretreatment group showed that: After simulated fast buoyancy ascent escape,the lung tissue edema in DCS experimental rats was significant,with the wet to dry weight ratio of the lung tissue increasing from(4.693 ± 0.142)to(6.398 ±0.203)(P < 0.001),The lung tissue showed severe alveolar structure destruction,fusion,and hyperemia,and pulmonary interstitial cells were edema,with significant hyperemia.Liver tissue is severely congested,and liver cell structure is disordered with a large area of bubble like change.But no obvious pathological changes in brain tissue.Nicotinflorin can effectively improve the damage of alveolar structure,pulmonary interstitial thickening and edema,and severe hyperemia of lung tissue caused by DCS,which reducing the wet to dry weight ratio of lung tissue from(6.398 ± 0.203)to(5.472 ± 0.186)(P<0.001)and reducing the pathological score of lung tissue from(3.177 ± 0.245)to(1.330 ± 0.194)(P<0.001).Nicotiflorin can effectively improve liver tissue congestion,reduce the ballooning area of liver cells,and reduce the pathological score of liver tissue from(2.480 ± 0.204)to(1.270 ± 0.118)(P<0.01).There were no significant pathological changes in the brain tissues of rats in the normal pressure control group,DCS group,and nicotiflorin group.The above results suggest that nicotiflorin has a certain degree of improvement on acute lung injury and acute liver injury caused by DCS.3.The effect of Nicotiflorin preventive administration on Inflammatory Factor TNF-α,IL-1β,IL-6 and Cell Adhesion Factor ICAM-1 in Lung Tissue of DCS Induced by fast buoyancy ascent escapeThe measurement results of TNF-α,IL-1β,IL-6,and ICAM-1 in the lung tissues of rats in each pretreatment group showed that: after simulated fast buoyancy ascent escape,the levels of TNF-α,IL-1β,IL-6 and ICAM-1 m RNA and protein in the lung tissue of experimental rats in the DCS group were significantly increased(P<0.001).Nicotinflorin at a dose of 20 mg/kg can inhibit the increase in the m RNA and protein levels of TNF-α,IL-6,and ICAM-1(P<0.001),and reduce the protein expression level of IL-1β in lung tissue(P < 0.05).However,there was no statistically significant difference in the inhibitory effect of nicotine on IL-1β m RNA expression(P=0.584).The above results suggest that inhibiting the expression of proinflammatory factors and adhesion factors in lung tissue may be one of the mechanisms of nicotine in improving DCS mediated acute lung injury.4.Persistent protective effect of therapeutic administration of nicotiflorin on acute lung injury induced by fast buoyancy ascent escape in DCS ratsTo observe the sustained protective effect of nicotiflorin on acute lung injury in experimental rats within 24 hours after simulated fast buoyancy ascent escape.The result show that: Injecting 20 mg/kg of nicotiflorin into experimental rats within 20 minutes after simulated fast buoyancy ascent escape can reduce the DCS induced increase in lung wet/dry weight ratio within 24 hours(P < 0.001).Nicotiflorin inhibits the significant expression of TNF-α m RNA and protein in rat lung tissue at 2and 12 hours(P<0.05).Nicotiflorin exhibited a sustained inhibitory effect on IL-1βprotein expression in DCS rats within 24 hours,and significantly inhibited IL-1β at its peak at 6 hours(P < 0.05).Nicotiflorin can also continuously inhibit the significant expression of IL-6 in DCS rats within 24 hours,and effectively inhibit the significant expression of ICAM-1 m RNA and protein in DCS group rats at 2 and 12hours(P<0.05).After escape,nicotiflorin administration can continuously alleviate the inflammatory reaction in the lungs of DCS experimental rats,which suggests that nicotine has a certain therapeutic effect on simulating rapid upward escape leading to DCS.To sum up,nicotiflorin has a significant protective effect on DCS caused by simulated fast buoyancy ascent escape,which can significantly improve the symptoms of nervous system injury and respiratory system injury caused by DCS,reduce the incidence rate and mortality of severe DCS,improve the acute lung injury and acute liver injury caused by DCS,and inhibit the expression of inflammatory factors and adhesion factors in lung tissue after DCS onset;Therapeutic administration can inhibit the deepening of pulmonary edema caused by DCS and the expression of inflammatory factors and adhesion factors in lung tissue within 24 hours.The results of this study provide an important basis for the application of nicotiflorin in the prevention and treatment of DCS caused by fast buoyancy ascent escape,and also provide a new way to expand the utilization of Carthami Flos resources. |
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