【Abstract】Objective To investigate the role of VEGF and its soluble VEGF receptor ( sVEGFR-1) in pathogenesis of acute lung injury ( ALI) induced by immersion in seawater after open chest trauma. Methods Sixteen hybridized adult dogs were randomly divided into control group and seawater group. The control group only suffered from open chest trauma, whereas the seawater group were exposed to seawater after open chest trauma. Blood samples were collected at the 0, 2, 4, 6, 8 h after trauma for measurement of white blood cell count, arterial blood gas, plasma osmotic pressure ( POP) , electrolyte concentration, IL-8, vWF, VEGF and sVEGFR-1 levels. The lungs tissue and BALF was collected at 8 h after trauma. Pathological changes of the lung was observed under light microscope by HE staining. Meanwhile VEGF and sVEGFR-1 levels were measured in BALF and lung tissue homogenate. Total protein concentrations in plasma and BALF were measured to calculate the pulmonary penetration index ( PPI) . Results The lung of the seawater group showed interstitial mononuclear cell and neutrophil infiltration, interstitial edema, and vascular congestion. VEGF and sVEGFR-1 were significantly increased in the plasma, while VEGF was significantly reduced in the lung tissues and BALF. The levels of IL-1β, IL-8 and vWF, just as the level of VEGF, were significantly increased in the plasma. Meanwhile, the POP and electrolyte concentration were significantly increased. In the plasma, the responses of VEGFs during the early onset of ALI induced by immersion in seawater after open chest trauma were consistent with the POP and PPI. Conclusions High plasma levels and low BALF/ lung tissue levels of VEGFs is a distinguishing characteristic during the early onset of ALI induced by immersion in seawater after open chest trauma. VEGF may be a novel biomarker which has an important role in the development of ALI.
Objective To investigate the protective effects of ulinastatin on acute lung injury ( ALI)induced by seawater drowning in rats. Methods Thirty male SD rats were randomly divided into three groups, ie. a control group, a model group, and an ulinastatin treatment group. The rats in the model group and the ulinastatin treatment group received intratracheal artificial seawater ( 4 mL/kg) instillation. Then the ulinastatin treatment group received ulinastatin ( 100 000 U/kg) injection after infusion of seawater while the model group received an injection of same amount of saline. The rats were sacrificed at 4 hours after instillation. The pathological changes of lung were evaluated by hematoxylin-eosin stain under light microscope. Lung wet/dry weight ratios were measured to assess the level of pulmonary edema.Concentrations of tumor necrosis factor ( TNF) -α, interleukin ( IL) -1β, IL-6, and IL-10 in bronchoalveolar lavage fluid ( BALF) were detected by enzyme-linked immunosorbent assay ( ELISA) . The myeloperoxidase activity in lung tissue homogenates were measured by colorimetric method. Results Ulinastatin treatmentsignificantly relieved the decline of PaO2 and lung pathological changes, inhibited myeloperoxidase activity,and reduced lung wet/dry weight ratios. Ulinastatin also inhibited the release of TNF-α, IL-1β, and IL-6,whereas increased the expression of IL-10 simultaneously. Conclusion Ulinastatin attenuates seawater induced ALI, which may be related to its inhibitory effects on inflammation reaction through regulating cytokine secretion.
Objective To investigate whether sodium tanshinone ⅡA sulphonate ( STS) treatment attenuates pulmonary edema of seawater drowning ( PE-SWD) , and examine the effects of STS on Na-KATPase(NKA) in PE-SWD. Methods Thirty-six rats were randomly divided into there groups, ie. a normal group ( NG) , a seawater group ( SG) , and a STS treatment group ( TG) . The rat model of PE-SWD was established by seawater instillation. PaO2 , histological changes of lungs, lung wet /dry weight ratio ( W/D) ,pulmonary microvascular permeability ( PMVP) , and NKA activity were detected. Western blot were used to test the effects of STS on NKA-α1 expression. Results Seawater instillation decreased PaO2 and the expression of NKA, while increased W/D ratio and PMVP. At 2 h after seawater instillation, the PaO2 in the TG group were significantly higher than those in the SG group, and peaked at 4 h after seawater instillation.Histological examination showed that there were hemorrhage, edema, markedly thickened alveolar wall, and infiltration of inflammatory cells in alveolar spaces in the SG group, but lung injury was significantly alleviated in the TG group. W/D ratio and PMVP in the TG group were significantly lower than those in the SG group. Additionally, NKA activity and NKA-α1 expression were significantly higher in the TG group than those in the SG group. Conclusion STS treatment can attenuate pulmonary edema of seawater drowning which may be related with up-regulating Na-K-ATPase activity and expression.
目的 建立犬开放性气胸海水浸泡的实验模型 ,探讨实验动物早期死亡原因。 方法 2 0条健康成年杂种犬随机分为两组。对照组 :实验动物受伤后直接观察 ;实验组 :动物受伤后置入人工配制的海水中。监测血流动力学、呼吸、血液渗透压、血液电解质、动脉血气变化以及肺部病理改变。 结果 实验组死亡率明显高于对照组 ,平均生存时间为 45分钟。实验组经海水浸泡后有急性呼吸和循环功能衰竭、严重电解质平衡紊乱、高渗血症、重度肺损伤以及严重代谢性和呼吸性酸中毒。 结论 开放性气胸后海水浸泡可引起一系列严重的病理生理变化 ,其结果是导致实验动物早期死亡的重要原因。
To observe the effect of chitosan/alginate (CTS/ALG) dressings on wound immersed in seawater. Methods Twenty-five healthy SD rats weighing 250-300 g were used to establ ish skin wound model through cutting 1.8 cm circle-shaped wound along spine bilaterally. The left side served as experimental group, and the right side as control group. The wounds were immersed in the prepared artificial seawater for 1 hour, then the experimental group was treated with CTS/ALG dressings, while the control group was treated with sterile gauze. Gross observation was performed andwound heal ing time was recorded. At 3, 5, 7, 10 and 12 days after operation, 2 cm × 2 cm skin tissues including the wounds were removed and underwent HE staining and immunohistochemistry staining using Envision method. Histological change of wound and expression of EGF receptor (EGFR) and bFGF were observed. Results In the experimental group, wound inflammatory response was sl ight and incrustation shrinked faster, while the incrustation in the control group shrinked slowly. The wound heal ing time of the experimental group and the control group was (11.68 ± 0.57) and (12.51 ± 0.54) days, respectively, suggesting there was a significant difference between two groups (P lt; 0.05). In the experimental group, granulation tissue prol iferation, cell infiltration, collagen tissue prol iferation, wound shrinkage and epithel ization appeared at 3 days after operation; regularly l ined collagen tissue, complete epithel ization and occurrence of skin appendages were observed at 10 days after operation; complete wound heal ing was noted at 12 days after operation; while in the control group, at the corresponding time point, late cell infiltration and epithel ization were observed and granulation tissue with ulcer was noted. Immunohistochemistry observation: high expression of bFGF in vascular endothel ial cells and interstitial fibroblasts and high expression of EGFR in vascular endothel ial cells were observed in the experimental group at 3 and 5 days after operation, and their expressions were low at 7, 10 and 12 days after operation; while in the control group, there were no or low expression of bFGF and EGFR at the same time point. Conclusion CTS/ALG dressings can promote the heal ing of wound immersed in seawater, but its mechanism needsfurther study.
ObjectiveTo establish pig abdomen bullet wound model in seawater immersion condition and to analyze injury characteristics. MethodsTwenty Xishuangbanna pigs were randomly divided into seawater immersion group and control group,with 10 in each group.The left lower quadrant anti McBurney point of the pig semi-floating in the seawater was shot by using domestic 81-1 assault rifle at the distance of 10 meters,which were salvaged out of seawater at 60 minutes after injury in the seawater immersion group.The pigs in the control group were treated same as the seawater immersion group except seawater immersion.The mean arterial pressure (MAP),rectal temperature (RT),heart rate (HR),respiratory (R),white blood cell count (WBC),and C-reactive protein (CRP) were tested at 1 h,4 h,8 h after injury.The death of pig was observed. ResultsThe pig abdomen bullet wound models in the seawater immersion condition were successfully established.① Compared with the control group,the MAP and RT were significantly decreased at 1 h,4 h,8 h after injury,the HR or the R was significantly decreased at 4 h or 8 h after injury respectively in the seawater immersion group.② Compared with the normal value,the WBC obviously rose at 4 h and 8 h after injury,the CRP obviously rose at 1 h,4 h,and 8 h after injury in both two groups.Compared with the control group,the WBCs were significantly increased at 4 h and 8 h after injury (P<0.05),the CRPs were significantly increased at 1 h,4 h,and 8 h after injury (P<0.05) in the seawater immersion group.③ The mortality in the seawater immersion group (50%) was significantly higher than that in the control group (20%,P<0.05). ConclusionThe injury is more serious,the infection time is earlier,and the infection degree is aggravated,the mortality rate is higher for pig abdomen bullet wound model in seawater immersion condition.
With the growth of offshore activities, the incidence rates of seawater drowning (SWD) induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) increase significantly higher than before. Pulmonary interstitial edema, alveolar septum fracture, red blood cells, and inflammatory cells infiltration can be seen under light microscope in the pathologic changes of lungs. The major clinical manifestations are continual hyoxemia and acidosis, which lead to a severe condition, a high death rate, and a poor treatment effect. Bone marrow mesenchymal stem cells are capable of self-renewal, multilineage differentiation and injured lung-homing, which are induced to differentiate into alveolar epithelial cells and pulmonary vascular endothelial cells for tissues repairing. This may be a new way to treat SWD-ALI and SW-ARDS.
ObjectiveTo improve the seawater-drowning-induced lung injury model in rats, and investigate the protective effect of resveratrol against seawater-drowning-induced lung injury and its mechanism.MethodsA total of 112 SD healthy rats were randomly assigned into 5 groups: a control group (Group C, n=8), a seawater drowning group (Group S, n=32), a resveratrol prophylactic treatment group (Group S+R, n=32), a resveratrol group (Group R, n=8), and an endotracheal intubation group (Group E, n=32). A modified endotracheal intubation model was developed, and endotracheal intubation was used instead of tracheotomy. Blood gas analysis was performed on the abdominal aorta at each time point, then the rats were sacrificed to obtain their lungs. Lung wet-to-dry ratio (W/D), malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO) and cysteinyl aspartate specific proteinase (Caspase-3) were measured by enzyme linked immunosorbent assay. The histological sections of rat lungs were stained with haematoxylin-eosin. Groups S+R and R were pretreated with resveratrol (50 mg/kg) through intragastric administration for 3 days; then models were established and the rats were sacrificed 24 hours after the last intragastric administration.ResultsAfter seawater perfusion, arterial oxygen pressure decreased and arterial carbon dioxide pressure increased in blood gas analysis of rats, MDA content increased, MPO and SOD activity decreased, caspase-3 content and W/D ratio increased, as well as lung tissue pathological damage. The resveratrol pretreatment group showed the same change trend, but the damage degree was relatively light.ConclusionsSeawater perfusion can induce respiratory failure, pulmonary edema and hemorrhage in rats. Lung tissue apoptosis may occur when seawater submergence causes lung injury. Resveratrol pretreatment can ameliorate hypoxia and pulmonary edema in rats.
Seawater drowning leads to acute lung tissue structure injury, lung ventilation and air exchange dysfunction, acute pulmonary edema, and even acute respiratory failure. The pathogenesis of seawater induced acute lung injury is complex, involving inflammatory response, pulmonary edema, pulmonary surfactant, oxidative stress, apoptosis and autophagy. Timely and effective treatment is the key to reduce the mortality and disability rate of patients with seawater induced acute lung injury. This article summarizes the research progress in the pathogenic mechanism and treatment strategy of seawater induced acute lung injury, aiming to provide reference for the comprehensive treatment of seawater induced acute lung injury patients in clinical work and subsequent related research.