| [Objective]This study is based on the understanding of chronic injury such as chronic inflammation, oxidative damage and vascular endothelial damage on human body caused by submarine harmful gas environment. We observe the effect of Yifei Huoxue Granule on rabbits against the influence of the special environment on their blood and lung tissue.The submarine environment is a special environment, with some common harmful gases such as carbon monoxide, carbon dioxide, and xylene often found exceeding the national military standard range after long-term submergence. Working in this environment, submariners will inevitably inhale the harmful gas. Some irritant gases absorbed by tracheal mucous membrane surface stimulate the vagus nerve, and at the same time, dissolved in wet airway can directly stimulate the contraction of respiratory smooth muscle, resulting in the decline of lung function. Meanwhile, the stimulation of harmful gas causes damage to pulmonary vascular endothelial cells, cause the white blood cell and platelet adhesion, harmful substances infiltration, and macrophages, neutrophils, cytokines interactions induce chronic inflammation. Harmful gas such as xylene can increase oxygen free radicals in the body and the imbalance of free radical metabolism can lead to lipid peroxidation damage.Yifei Huoxue granule, originated by Academician Dong Jianhua based on his clinical experience, is a compound promoting blood circulation and removing blood stasis for lung mainly used for the treatment of chronic pulmonary heart disease and pulmonary hypertension. The latest research shows that it can make blood vessels diastolic, reducing the pulmonary arterial pressure. Modern medical research shows that the large amounts of flavonoids contained in astragalus can eliminate oxygen free radicals, and astragalus polysaccharides can stimulate the immune system in many ways, reduce the production of inflammatory cytokines. Moreover, codonopsis pilosula, containing a variety of polysaccharide material and amino acids, can significantly stimulate the reticuloendothelial system, enhance its phagocytic function, and thus improve human immunity after use with codonopsis pilosula. For the functions of the compound, including reducing the production of inflammatory cytokines, removing excess oxygen free radical, protecting blood vessel, and reducing vasoconstriction, consistent with the aim of protectinig human body from submarine environment injury, we research the protective effects of Yifei Huoxue granule on rabbits under submarine environment.With the development of the nautical medicine and the rapid construction of naval modernization, the guarantee of submariners’ health care, improving their immune functions, establishing first-class prevention mechanism and enhancing their adaptability, is of great importance. The combination of the military medicine and traditional Chinese medicine to study the effect of submarine environment on rabbits and the protection of Yifei Huoxue granule makes up for weakness of research on chronic lung injury and pathological features of animals chronic inflammatory reaction under submarine environment at home and abroad. It provides theoretical foundation for studying the protective effects of Yifei Huoxue Granule on submariners’ pulmonary vessel endothelial cells and pulmonary function, and also opens up a new idea for studying the protection from lung inflammation, oxidative damage and vascular endothelial injury. The study is conducive to the development of modernizing traditional Chinese medicine and its application in military medicine, directing the future research of traditional Chinese medicine.[Method]We choose monoxide, carbon dioxide and xylene cabin to simulate the the common harmful gas in submarine environment, by referring to the military standard of "Conventional submarine cabin air composition allowable concentration"(GJB11.3-91), and establish animal model through the HOPE-MED8050series dynamic inhalation system.The New Zealand white rabbits were randomly divided into four groups,15rats in each group.(1) Model group, with normal saline and simulated submarine environment.(2) Dexamethasone group (group DM), with dexamethasone and simulated submarine environment.(3) Yifei Huoxue granule group (YFHXG):, with Yifei Huoxue granule and simulated submarine environment.(4) The control group,with normal saline and normal indoor environment. Rabbits in each group were fed corresponding drugs for14days, with14-day exposure in corresponding environment,4hours a day.After14days, we sampled auricular veins blood of the rabbits for upper serum, and used rabbit lung tissue to make immunohistochemical staining slice and lung homogenate grinding fluid after putting the rabbits to death. Rabbit serum and lung homogenate tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), and endothelin-1(ET-1) were detected through radioimmunoassay. Oxidation reduction method and nitrate reductase assay method were respectively applied to determine superoxide dismutase (SOD) content and NO concentration\Lung tissue TNF-α and IL-6immunohistochemical staining slice were observed under light microscope.[Results] In the aspect of chronic inflammation injury and oxidative damage, compared with those in the control group, the activity of SOD in serum and lung homogenate in model group decreased significantly (P<0.05), TNF-α, IL-6level increased significantly (P<0.05), Compared with those in the model group, the SOD activity in serum and lung homogenate increased significantly in groups YFHXG and DM (P<0.05), and TNF-α, IL-6decreased significantly (P<0.05). SOD activity in lung homogenates of group YFHXG increased more significantly than that in the group DM (P<0.05). On the other hand, group DM bring down theserum TNF-α and lung tissue homogenate IL-6level was better than group YFHXG (P<0.05). There are significant differences in the pulmonary tissue immunohistochemistry sections between each group (P<0.01). In the control group, TNF-α and IL-6staining was weak positive (+), model group showed strong positive (+++), in which the cell membrane or cytoplasm have strong brown staining small particles, groups YFHXG and DM as the positive (++).As for the vascular endothelial injury, compared with those in control group, the content of NO in serum and lung tissue homogenate decreased significantly in model group (P<0.05) and ET-1significantly increased (P<0.05), while the content of NO in serum and lung tissue of rabbits in YFHXG group and DM group significantly increased and the secretion of ET-1level reduced, compared with those in model group (P<0.05). The content of NO YFHXG group increased more obviously than that in the dexamethasone group (P<0.05).[Conclusion]Based on the above experiments, we can conclude that the submarine composite gas environment with carbon monoxide, carbon dioxide and xylene can cause chronic inflammatory reaction and oxidative damage on rabbits and affect the vascular endothelial function. Exerting a significant protective effect on rabbits, Yifei Huoxue granule can obviously reduce the inflammatory reactions such as TNF-α factor release, the chronic inflammatory reaction, observably improve the level of SOD and the antioxidant ability of rabbits, and can adjust NO and ET-1level in rabbits, reduce vasoconstriction, prevent vascular smooth muscle remodeling.In this study, the following conclusions can be reached:(1) After long-term exposure to low-concentration harmful gas in submarine environment, chronic inflammatory reaction with pathological change inevitably appeared on rabbits..(2) After long-term exposure to low-concentration harmful gas in submarine environment, the secretion of rabbit vascular endothelial become out-of-balance, resulting in vascular regulation factor secretion disorder.(3)The long-term exposure to low-concentration harmful gas in submarine environment has certain influence on oxygen free radical in vivo metabolism, and oxidative damage to their bodies to some extent.(4) In the simulated submarine harmful gas environment, Yifei Huoxue granule can reduce the inflammatory cytokines contention in rabbits and alleviate the infiltration of inflammatory cells.(5) In the simulated submarine harmful gas environment, Yifei Huoxue granule can balance the disorded secretion of vascular endothelial dysfunction, and reduce the risk of high blood pressure.(6) In the simulated submarine gas environment, Yifei Huoxue granule can significantly improve oxygen free radical scavenging activity in the rabbits especially in lung tissue, reducing the risk of the oxygen free radicals excessive accumulation in vivo. |
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