| SECTION 1:The Protection of Montelukast in Rat Trachea TransplantationObjective:Montelukast is a new type of LTB receptor antagonist that has been found to have anti-inflammatory effects and to play an important role in dilating bronchi.However,the effects of montelukast on transplanted lung have not yet been reported.This study compared the inflammation and expression of related proteins to explore the effects and mechanisms of montelukast on transplanted trachea.Methods:Recipients were randomized to receive an oral administration of montelukast suspension(3 mg/kg;experimental group),dexamethasone(1 mg/kg;DEM group),or normal saline solution(2 mL/kg;control group)for 4 weeks after trachea transplantation.The cytokine concentration in the serum of the recipients was determined after sacrifice.Histopathologic evaluation,including tracheal occlusion rate,was performed with hematoxylin-eosin staining and Masson staining.The expression of CASP1,NOX4,PAK CAT,LT4R1 was assessed by immunohistochemical analysis.Results:Histopathologic evaluation showed inflammatory cell infiltration,concentric or eccentric lumen stenosis or occlusion in the control group;the severity of which was greater than that in the other two groups.The tracheal occlusion rate in the experimental group,DEM group and control group were 54.46±29.84%,72.01±26.41%,72.63±33.71%.The levels of LTB4 and TGF-? in the serum of the RES groups were lower than those in the control group and DEM group.The expression of LT4R1,NOX4,PKA CAT and CASP1 in the experimental group was 42.86%,61.90%,66.67%and 52.38%lower than that in the control group,respectively,and was proportional to tracheal occlusion rate.Conclusions:Based on these findings,we propose that the treatment with montelukast affords a certain degree protection of anti-inflammation to transplanted rat trachea in the long stages after transplantation,which can reduce the incidence of bronchiolitis obliterans after tracheal transplantation.SECTION 2:The Role of Epithelial-mesenchymal Transition in Bronchiolitis Obliterans after Lung Transplantation Objective:Recent findings have indicated that epithelial-mesenchymal transition is involved in the process of multiple airway remodeling diseases.We hypothesized that bronchiolitis obliterans after lung transplant is associated with epithelial-mesenchymal transition.This study compares the expression of relative proteins of epithelial-mesenchymal transition in allograft and isograft to explore the relationship between this pathway and bronchiolitis obliterans in rats.Methods:We performed an orthotopic left pulmonary transplant model using the tri-cuff vascular anastomosis method.The left lungs from Fischer 344 rats were transplanted into Lewis recipients.The recipients were treated with ciclosporin and lipopolysaccharide at a certain time.The grafts were collected 90 days after transplantation.The histopathology,including the severity of fibrosis,were evaluated by hematoxylin-eosin and Masson's trichrome staining.The expression of Vimentin,E-cadherin and other proteins was accessed by immunohistochemistry.The concentrations of TGF-P and TNF-a in serum were analyzed.Results:The pathology showed that the allotransplant model developed bronchiolitis obliterans 90 days after the operation.The percentages of a high expression of Vimentin and mTOR in the allograft group were higher than in the isograft group,respectively,P<0.01.The SF score was highest in the allograft and was positively correlated with the expression of the Vimentin?E-cadherin and mTOR proteins.The level of serum TGF-? in experimental group was higher than that in control group.Conclusions:This model could simulate human bronchiolitis obliterans after lung transplantation.The expression of epithelial-mesenchymal transition associated proteins in post-transplantation was regulated,suggesting that activation of the epithelial-mesenchymal transition pathway might be involved in the occurrence and prognosis of bronchiolitis obliterans. |
PDF Full Text Request