The Effect Of The Wnt/?-catenin Pathwayon The Process Of ARDS Induced By Sepsis

Backgrounds: The acute respiratory distress syndrome is characterized with progressive hypoxemia which caused by kinds of pathogenic factors inside and outside the lungs include infection, trauma, poisoning, acute pancreatitis and shock except Cardiogenic. We have little known about the Pathophysiological mechanisms of ARDS. ARDS is characterized with the injury of epithelial cells, the injury of endothelial cells and the increased of blood capillary permeability, the inflammatory cells infiltration and excessive inflammatory mediators, collagen deposition, pulmonary edema or alveolar collapsion, the alveolar septum incrassation and lung fiber formation. Studies have found that the wnt/?-catenin pathway was activated abnormally in the process of epithelial cells injury and lung fiber formation. This may prompt that the Wnt/?- catenin signaling pathway participate in the damage process of ARDS. Considering that the Wnt/?-catenin pathway may participate in the process of ARDS, we take this pathway as a target in this project. Using the CLP technique to establish the ARDS model induced by sepsis; injecting the inhibitor of XAV939 by intraperitoneal to inhibit the Wnt/?-catenin signaling pathway. To observe the effect of the wnt/?-catenin pathway on process of ARDS induced by sepsis.This will provide an important theoretical basis for the new treatment strategies of sepsis by inhibitting the Wnt/?-catenin signaling pathways.Obejectives: To discuss the effect of the wnt/?-catenin pathway on process of ARDS induced by sepsisMethods:Anesthetized SD rats(male,250±10g)were used to establish the model. Fifty SD rats rats were divied randomly into three groups. The control group:a total of ten, these rats received the same procedures except perforation and ligation; the CLP group:a total of twenty, the rats recevied CLP, the procedures will be detailed in the experiment part; the CLP+XAV939 group: a total of twenty, on the basis of sepsis model established by CLP,these rats were injected XAV939 by intraperitoneal at the fisrst and second day, the procedures will be detailed in the experiment part. To observe the difference of the rats activities as well as the mortality rate between the control group,the CLP group and the CLP+XAV939 group. Rats were sacrificed after 48 hours.Using the WB to test the change of the?-catenin,the Cyclin D and the TNF-?in the lung tissue; Using the HE pathological dyeing technonlogy to observe the change of pathological damage degree; using the IHC and IF to test the expression quantity and the main parts of the key proteins in the lung tissue about the wnt/?-catenin signaling pathways; Using Real-time PCR to observe the change of ?-catenin at the genetic level.Results: The sepsis model had established successfully by CLP. Comparing the CLP group with the control group we can find these differences as follows : the mortality rate of the CLP group was 40% while the control group was 0 within 48 hours; the CLP group rats are lethargy;and the activity of the CLP group are decreased significantly;the weight of the CLP group lost about 20%; the alveolar edema and collapse, the alveolar interval became broadening, a large number of inflammatory cells infiltration, pulmonary vascular engorgement obvious; the Inflammatory cytokines of TNF? increased significantly in lung tissue compared with the control group; the proteins of ?-catenin and cyclin D were increased significantly than the control group; a large amounts of ?- catenin proteins can be found in inflammatory cells, epithelial cells and the bronchial epithelial cells inside the lung by IHC; the protenin of LRP5/6 can be visible seen by IF; the m RNA level of ?-catenin is higher than the control group.In the CLP+XAV939 group:the mortality rate of the CLP +XAV939 group was 0; the weight lost about 10% which is less than the CLP group;the activity of the rats is increased compared with the CLP group; the pathology damage degree reduced Significantly compared with the CLP group; the TNF-?,the ?-catenin protein and the Cyclin D in lung tissue were decreased significantly compared with the CLP group; the m RNA level of ?-catenin was decreased significantly than the CLP group while it has little difference compared with the control group.Conclusion: In this project, we find that the Wnt/?-catenin signaling pathway participate in the process of ARDS induced by sepsis; injecting XAV939 by intraperitoneal to inhibit the Wnt/?-catenin signaling pathway can reduce the lung tissue damage degree. This provide an important theoretical basis for the new treatment strategies of sepsis which will make great significance to improve the high mortality that caused by sepsis.