ABSTRACT
Lung transplantation is the ultimate treatment of end-stage lung disease. After transplantation, the 1-year survival rate is 80%, while the 5-year survival rates remaines at around 50% mainly due to bronchiolitis obliterans syndrome (BOS). BOS is regarded as a fibrosing process in the small airways leading to irreversible airway obstruction. A lot of factors are involved in the development of BOS, such as Ischemia/reperfusion injury, infections, oxidative stress, and acute rejection, etc. Studies have shown that early diagnosis of BOS may improve outcome. It is valuable for the long-term survival of lung transplantation to find out several predictors for the BOS. This article reviews the current state of knowledge on predictors for BOS.
ABSTRACT
Objective To imitate the pathological process of bronchiolitis obliterans(BO) post lung transplantation and in-vestigate the phenomenon of epithelial-mesenchymal transition ( EMT ) in small airway epithelial cells and its relation to BO . Methods We established the rat model of allogeneic orthotropic left lung transplantation with grafts from F 344 rats transplanted to Lewis rats by the Tri-cuff anastomosis.Then rats were daily injected intraperitoneally with cyclosporine (5 mg· kg-1 · d-1 ) for 10 days, intratracheally applied with lipopolysaccharide(0.5 mg/kg) at the 28th day and killed at the 90th day post-surger-y.We observed the histological structure of the lung grafts by HE and Masson staining , detected E-cadherin and Vimentin ex-pression in lung grafts and normal ones of F344 rats by immunohistochemistry, then analyzed the relation between small airway remodeling and the alterations in EMT markers expression .Enumeration data was analyzed with Fisher exact test and Spearman rank correlation was applied in correlation analysis .Results We found inflammatory cell infiltration , fibroplasia of bronchiole walls and significant lumen stenosis in lung graft mesenchyma.In lung grafts, the positive expression of E-cadherin was 5(total 13), which was significantly lower than that in normal lungs(7/8, P<0.05), and conversely the positive expression of Vim-entin was higher than normal ones(10/13 vs 2/8, P <0.05).The Spearman rank correlation analysis demonstrated that E-cadherin expression bear a negative correlation with Vimentin expression(r=-0.750, P<0.01).Conclusion Our study established a disease model imitating the pathological process of BO .And EMT was observed in small airway epithelial cells of the BO-exhibited lung grafts, indicating that EMT was involved in the process of BO airway remodeling .Thus it may reveal no-vel therapeutic targets for BO post lung transplantation by further investigation into the mechanism and pathological significance of EMT in small airway epithelial cells.