| Decompression sicknes(s DCS), pressure related injury , is that illness which follows a reduction in environmental pressure sufficient to cause the formation of bubbles from gases dissolved in body tissues. DCS can be divided into two types: Type I DCS (mild) is characterized by pain, pruritus, skin marbling and lymphatic involvement; while Type II DCS (severe) includes all patients who have pulmonary symptoms, hypovolemic shock or the more serious symptoms or signs of nervous system involvement. Acute severe decompression sickness has high mortality in the worldwide because of few effective treatment.Unsafe hyperbaric exposure is known to affect the system haemorheology of animal, impairing the capillary blood vessel and tissue around, and causing inflammatory changes like hemorrhage and exudation. At that time, platelet aggregation was observed in the lung. Platelets, active particles, are known to relate with a variety of pathological processes and diseases now. In addition to procoagulant role, the platelet is also involved in thrombosis and inflammation by the ways of adhesion and interaction with other inflammatory cells through many proinflammatory factors they secreted. Previous researches have investigated the changes of platelet count and membrane glycoproteins in different diving modes, including unsafe decompression. But there is no mechanism reported. In present study, we would discuss the role of platelets in the pathogenesis of acute decompression sickness with pulmonary injury from two aspects: inflammatory signaling and metabolic regulatory networks.Methods:In this study, we first seleted New Zealand rabbits and SD rats as the experimental model of acute DCS by unsafe rapid decompression (RD) from 0.7 MPa. Platelet count were detected at 15min, 1h, 3h, 24h after decompression, together with membrane glycoproteins expression detected by flow cytometry with FITC linked polyclonal antibody. The lung injury were observed by pathological staining, and the expression of Mac-1, IL-8, MCP-1, and MMP-9 in the lung tissue were detected with the immunohistochemical (IHC) method. The concentrations of TXA2, 6-k-PGF1alpha, PAF, sCD40L, sP-selectin, and TSP-1 in serum were determined separately with sandwich enzyme-linked immunosorbent assay (ELISA) kit. In addition, Metabolic fingerprinting of DCS animals in serum was firstly obtained by application of high-resolution proton Nuclear magnetic resonance (NMR) technology. With multivariate data analysis, some potenial biomarkers were found from changed metabolic pattern related with DCS. Through conventional biochemical methods, the content of glucose, free fatty acids, 3 - hydroxybutyric acid, lipoprotein a, and pyruvate dehydrogenase were determined.Main results:1. During the exposure profile of 7ATA staying for 60min and decompression within 5min, we successfully built a New Zealand rabbit model of acute severe decompression sickness, with rabbit mortality rate 32.5%. Precordial bubble sound ofâ…¢-â…£grade can be heard in rabbit after decompression, histopathological examination showing multiple organ intravascular bubbles, and light microscope examination revealing tissue bleeding, congestion, plasma exudation, cell degeneration and necrosis.2. After the rabbits experienced rapid decompression (RD), there were air bubbles observed in blood, together with significant platelet aggregation and platelet count (PC) decreased. The change of platelets after RD appeared at 30min post-decompression, and lasted for more than 24h. But the decreased count and decreased percent (%) of platelets showed no significant difference in death group and survival group of rabbits.3. The decline of PC in rabbits were also observed after slow decompression (SD). It continuously decreased and appeared significantly lower in the 24h post-decompression. The biggest difference of PC between RD and SD was the decreasing speed, the former is sharp, while the latter is steady. 4. The expression of platelet membrane glycoprotein CD41/61 and CD62p in rabbits were increased significantly after RD and continued to increase within 3h. Samely, the secretion of TXA2 from platelets was increased greatly (P<0.05).5. In rats after rapid decompression, reducing of the number of circulating blood platelets was observed, and continued to 2h after decompression (P <0.05). Slow decompression also resulted in circulating blood platelet count decreased, but showed insignificant differences. Histopathology showed acute inflammatory injury in lung such as alveolar hemorrhage, inflammatory cell infiltration, etc in rats after rapid decompression.6. In rats after rapid decompression, the concentration of PAF, sCD40L, P-selectin in rat serum were significantly increased (P <0.05, P <0.01), while that of TSP-1 was significantly lower (P <0.01). Immunohistochemistry showed that the expression of Mac-1, MMP-9 in the lung tissue increased significantly at 15min after RD, while MCP-1 expression in lung tissue increased at 3h after RD, but the expression of IL-8 fell in RD15min group.7. In this study, metabolic profiles via NMR-metabonomics showed markedly different between DCS animals and the controls.8. After PCA and OPLS-DA pattern recognition analysis, we found that glucose level in serum was significantly higher after hyperbaric exposure than that before exposure, which was more obvious after RD.9. In New Zealand rabbits after RD, lipid metabolism was enhanced because lipoprotein and lipid metabolite levels increased (P <0.05), while SD rabbits displayed no differences. In rats after RD, there were also shown a significant increase in ketone bodies.10. There were 23.5% minipigs showing obvious syptoms of decompression sickness after repeated exposure to 0.45 MPa for 6h following rapid decompression (1 min) for six months. The two-dimension emission computed tomograph (ECT) showed greater accumulation of isotone in femoral heads of exposed minipigs than that of controls, meanwhile pathologic examination proved that the feature of osteonecrosis had been existed.11. The platelet count (PC) of minipigs showed no markedly change in 1 month after repeated exposures, but progressive decrease in 3 month and 6 month (P<0.01). with increasing frequency of pressure exposures, Meanwhile, the increased blood viscosity at the low scissor rate (5.75 S-1) in 1 month and 3 month (P<0.05)were observed.12. 13 male patients of DON had accepted hyperbaric oxygen treatment for 3-32 times per person. There were 2 cases who exposed HBO over 30 times showing positive improvement in symptoms and/or X ray findings; while 11 cases less than 30 times showing no markedly change.Conclusions:Rapid decompression induces large amount of activated platelets by venous bubbles, leading to aggregation, secretion, formation of blood clots, bleeding and exudation in many tissues, in which the decreasing rate of circulating platelet count may be associated with the severity of decompression sickness. Mang activated platelets induced by rapid decompression activation, accumulate in the lung and release a large number of proinflammatory mediators and chemokines, which induce leukocyte and endothelial cell adhesion, causing inflammatory lung tissue. The activated platelets may participate in and mediate the inflammatory palmonary damage through PAF, CD40 / CD40L, P selectin signalings. The interaction among platelet- leukocyte and endothelial cell may play an important role in inflammatory injury of decompression sickness. Rapid decompression caused energy disorder, characterized by increase of glucose and lipid proteins and lipid metabolites, in which lipid metabolism level may be related with the severity of decompression sickness. Platelets which can secret PAF and other many lipid inflammatory mediators, may play an important role in the energy disorder caused by decompression sickness.
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