| Occurrence of decompression sickness (DCS) can always be found among both novice or inexperienced drivers and persons with all levels of training and experience when there is a sudden or excessively rapid reduction in ambient pressure. DCS manifestations range from simple joint pains to severe injury, including itching, arthralgia, paralysis or even death. The fundamental mechanism of DCS is known to be the formation of gas nuclei and the impairment caused by bubbles. The danger is not only due to the bubble blockage of the vascular, but also to a series of chemical reactions. So. it may present serious cardiopulmonary or neurological symptoms that can lead to death. Therefore, alternative methods are still required to prevent or attenuate symptoms when hyperbaric devices are delayed or unavailable.Simvastatin, one of the3-hydro-3-methylglutaryl coebzyme A (HMG-CoA) reductase inhibitors, is primarily used clinically for lowering hypercholesterolemia because of their inhibitory effects on hepatic biosynthesis of cholesterol at the mevalonate step. However, previous studies revealed that simvastatin has pleiotropic effects independent of its lipid-lowering actions, such as preserve endothelial integrity, reduce ischemia-reperfusion injury, and depress the interdependent inflammatory or coagulation cascades. Because intravascular decompression-induced bubbles can lead to endothelium damage, inflammation, edema formation and platelet aggregation during the development of DCS, we thus hypothesized that stimvastatin may attenuate the symptoms of DCS via its pleiptropic effects and provide a novel method for prevention of DCS.The objective of our study is to investigate the effect of stimvastatin preconditioning on DCS. Based on the above ideas, the study is divided into two parts:The first part is to explore the protective effect of stimvastatin preconditioning on DCS in rats. Because simvastatin may directly affect the animal’s body weight and thus influence the incidence of DCS. Meanwhile, the lipid-lowering effect may influence the incidence of DCS. The first part of the experiment is divided into two stages:①Investigate the effect of stimvastatin on the weight of the animals:Simvastatin was administered orally for two weeks (2mg/kg/d) in SD rats (n=10) and another10animals were used as the control group. Compared with the control group,the body weight of SIM group was significantly reduced after two weeks. The lipids and body fat not significantly change (P>0.05).②The second stage is to explore the protective effect of stimvastatin preconditioning on DCS in rats. According to the results of previous experiments, body weight of simvastatin group slightly higher than the control group. Two weeks later, the rats weighing300-310g were used in the experiment. Adult SD rats were treated with "700kPa-60min hyperbaric air exposure and3min decompression" profile. The morbidity and mortality of DCS, D/W weight of lung, protein in BAL and histologic examination were studied. We found that simvastatin significantly reduced the incidence of DCS from85.0%to45.0%(P<0.05) and postponed the onset of DCS (P<0.01). The D/W ratio of lung weight increased (P<0.05) and the total concentration of proteins in bronchoalveolar lavage (BAL) level decreased (P<0.05) in simvastatin treated rats. Histologic examination presented reduced changes in simvastatin-treated rats. These results show that stimvastatin preconditioning was beneficial for DCS, especially improve lung injury after decompression.The second part is to investigate the possible mechanism of stimvastatin preconditioning on DCS in rats. Animals were treated with the same profile as described in the second part and divided into two groups (the stimvastatin group and the control group, n=20in each group).30min after decompression, blood and lung were sampled to test the levels of MDA, TNF-a and EMPs. We found that simvastatin significantly reduced the levels of MDA in lung (P<0.05) and TNF-α in lung and blood after decompression (P<0.05). Levels of EMPs were also decreased after stimvastatin preconditioning in blood (P<0.05). We concluded that the protective effect of stimvastatin preconditioning on DCS may via the anti-oxidation, anti-inflammation and protected endothelial function.In conclusion, these results indicate that in animal models, simvastatin preconditioning(2weeks ahead of decompression) could effectively prevent the DCS, and the mechanism of its protection may be through the anti-oxidation, anit-inflammation and protected endothelial function. |
PDF Full Text Request