The Effect And Mechanism Of SecinH3on Sepsis Induced Acute Lung Injury

Acute lung injury is a common clinical syndrome in the ICU, and leads to higher mortality. It often occurs in patients with sepsis. In sepsis induced acute lung injury in the pathogenesis of microvascular leakage, and pulmonary edema, can increase the severity of the disease. In this process, is characterized by a significant barrier to the destruction of endothelial cells, increased permeability.Tight junctions between endothelial cells and endothelial cell adhesion barrier plays an important role in cell connections for many researchers found a number of important signaling pathway, and to improve the permeability of the drug, but in severe lung injury, not only the cell junction destruction or damage of endothelial cells themselves can also cause apoptosis in permeability. Thus protecting endothelial cells from damage, is to reduce the permeability of a base means.One kinds cytohesin Arf-GEFs inhibitors, secinH3, by blocking the activation of Arf6, thereby enhancing the connection between the cells. But SecinH3whether endothelial cells have a protective effect, there is no literature, therefore, in this paper, we cause lung injury in mouse models of sepsis, the application cytohesion inhibitor, secinH3, to treat sepsis caused lung injury, observe whether he has a protective effect on endothelial cells, as well as its vascular permeability and lung injury.Research MethodsMice were divided into two groups, sham group and the CLP group, CLP induced sepsis study the impact of the lungs to determine the CLP cause lung injury model results. The general situation was observed in mice, blood gas analysis, lung compliance, and lung biopsy, and mortality.Two mice were randomly divided into4groups:sham operation group, CLP group, SecinH3low-dose group, SecinH3high dose group. To determine whether the lower SecinH3permeability, reduce pulmonary edema. Observation Tabs:mouse blood gas analysis, lung compliance, and lung biopsy, and mortality. Protein, cells, a case of water leaks. And lung levels of proinflammatory cytokines. 3. The four group after24hours after the detection of lung derived endothelial cell status, transmission electron microscopy and blood levels of vWF. Superoxide dismutase and malondialdehyde and other indicators of oxidative stress, simultaneous detection of Nrf-2expression. In cultured human umbilical vein endothelial cells with LPS as an injury factor, research SecinH3on LPS-treated endothelial cells, flow cytometry apoptosis. And in vivo and in vitro studies of a DDC inhibitor of SOD SecinH3role.Result1. CLP surgery, mice, respiratory function, significant deterioration in lung compliance. Significant increase in mortality, lung HE staining, CLP surgery, severe pathological damage the lungs of mice, a large number of alveolar exudate cells. Widened alveolar septum.2In the CLP-induced lung injury model, SecinH3can improve postoperative mouse lung respiratory function, mouse blood and compliance have been improved, and lung biopsy has also been improved. Lung leukocytes, whole-cell exudation, and wet to dry ratio. Detection of proinflammatory cytokines showed that:the lungs of TNF and IL-6did not decline.3In the postoperative pulmonary electron microscopy showed that:mouse lung endothelial cells, endothelial cells after CLP, severe swelling. But SecinH3can improve endothelial cell swelling and protect endothelial barrier. In SecinH3use, blood levels of vWF sharp decline. Further studies showed that, SecinH3SOD activity can be increased, reducing the amount of MDA. Reduced apoptosis of endothelial cells. Immunoblotting experiments show:SecinH3by enhancing the expression of Nrf-2from play to reduce the effects of oxidative stress, Nrf-2is an important antioxidant factor. SOD inhibitor DDC experimental evidence:DDC can block SecinH3antioxidant.Conclusion1. CLP model can lead to acute lung injury, the damage model for lung function and microscopic pathology generally have a greater influence, is a better model of lung injury.2. SecinH3can reduce protein exudate cells after acute lung injury and pulmonary edema, exudate, reducing the permeability of the lung. But not reduce lung proinflammatory cytokine levels. 3. SecinH3Nrf-2by regulating the expression of increased SOD activity, reducing oxidative stress, thereby protecting the endothelial cells, reducing endothelial cell apoptosis.