| BackgroundSevere inhalation injury is still one of the leading causes of death of burn,and the mortality caused by acute respiratory distress or respiratory failure can be as high as50%.Now it is knowledged that in the early stage after inhalation injury, some cells in lung tissue,such as macrophages,neutrophils and vascular endothelial cells release a large number of acute inflammatory cytokines, which can induce not only a wide range of local organizations and severe lung inflammation even as respiratory dysfunction, but also lead to further excessive systemic inflammatory response and multiple organ failure.However, the multiple organ dysfunction caused by acute respiratory dysfunction is the direct reseaon that cause high mortality. On the current situation, there is no effective drug can reverse the progression of multiple organ dysfunction about clinical treatment. NF-κB pathway is known as a inflammatory signal transduction pathway,which encodes a variety of inflammatory transcription factors,chemokines,in the early stage of the inhalation injury,excessive activation of this pathway in macrophages and subsequent is closely related to the occurrence of systemic inflammatory response syndrome. Therefore,in order to reduce the high mortality caused by inhalation injury,it is necessary to focus on the suppression after inhalation injury of a large number of inflammatory cytokines which could cause multiple organ dysfunction in the early stage.1. A murine model of smoke inhalation injury in mice[ABSTRACT] Objective:To establish a murine model of smoke inhalation injury. Methods:Healthy BALB/c mice were selected and device that could cause smoke inhalation injury was customed. Pine sawdust and kerosene were selected as fuming material and six time periods, that were6min,8min,10min,12min,14min and16min were set up for mice inhaling smoke. Symptoms, survival rate in seventy-two hours, and pathological changes in lungs of dead mice were observed. Results:(1)Partial mice died in the course of inhaling smoke, and the respiratory rate were accelerated and activity were decreased in survival mice, but it got right in several hours.(2)Survival rate in seventy-two hours of the six groups were100%,97%,73%,52%,43%,and0.(3)Pathological analysis showed that in lungs of dead mice after smoke inhalation injury inflammatory cells infiltration,hemorrhage, and alveolar wall edema emerged at different levels. Conclusions:Inhaling smoke caused by Pine sawdust and kerosene could cause smoke inhalation injury at moderately severe levels for mice. The model was relatively easy to made and replicated and it was a relatively appropriated model for researching the smoke inhalation injury.2. Effect of the Activity of Macrophages and Nuclear factor-κB following smoke inhalation injury in mice[ABSTRACT] Objective:To explore the role of activity of macrophages and nuclear factor-kappaB insmoke inhalation injury and evaluates their possible effective mechanism. Methods:Forty-eight BALB/c were randomly divided into four groups: the normal group,group A,group B,group C.There were twelve mice in each group and smoke inhalation induced lung injury model were replicated.Depletion of macrophages was accomplished by administration of Liposomal encapsulated clodronate delivered via intratracheal for group B,while normal saline was delivered via intratracheal for group C. The survival rate in72hours was observed and lung tissues were collected from every viable mouse to observe pathological change and meassure the NF-κB virances by immunohistochemistry and inflammatory factor TNF-a by ELISA. Results:(1)The survival rate in72hours of group B was higher than other groups;(2)The pathological changes in lungs were also more evident of Bgroup;(3)The expression of NF-κB and changes of inflammatory factor has correlation with the quantity of macrophages. Conclusion:The activity of macrophage and NF-κB may play an important role in lung injury of smoke inhalation.3. The effects of Bortezomib to Inflammatory Signaling Transduction in Smoke inhalation induced-lung injury in mice[ABSTRACT] Objective:To explore the protective effect and possible mechanismof Bortezomib for multiple organs after smoke inhalation injury in mice. Methods: Smoke inhalation injury model were replicated.Bortezomib was administrated by intraperitoneal injection half an hour before injury,and12hours;24hours post injury.Then the survival rate in72hours and pathological changes on lung,heart,liver,kidney were observed. Histological scores of NF-κB p65with immunohistochemistry stain was evaluated,and the concentration of TNF-awas measured with enzyme-linked immunosorbentassay (ELISA). Results:Bortezomib could help to alleviate the degree of inflammatory affection in lungs, inhibit the activation of NF-κB p65,and lower the concentration of TNF-a in serum (p<0.05).Conclusions:The activation of NF-κB p65paticipated the course of smoke inhalation induced-lung injury,and Bortezomib could inhibit the activation of NF-κB p65,and the protective effect was remarkable for multiple organs when Bortezomib was administrated at12hours post injury. |
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