循环纤维细胞在ALI/ARDS损伤修复中的作用及预后价值研究

急性肺损伤/急性呼吸窘迫综合症（ALI/ARDS）死亡率高,预后差，肺损伤后纤维增生修复失控是影响其预后的主要原因之一。循环纤维细胞（CF）是一种新近发现来源于骨髓、具有成纤维细胞特性、表达CD45+Col-1+的白细胞亚群。CF具有迁移到损伤组织、多能转化特性,它可能参与了ALI修复,与ALI预后相关。本项目拟在LPS致ALI小鼠模型上采用GFP转基因小鼠骨髓移植示踪肺损伤后CF在CXCL12/CXCR4作用下由骨髓释放至外周血液迁移至肺部，研究CF数量与肺组织胶原沉积量、转化为肌成纤维细胞数量以及生存率之间的关系，阐明CF是参与ALI修复、影响ALI预后的主要细胞。临床实验拟选择ALI/ARDS患者探讨验证CF数量与疾病进展、病情严重程度、肺组织纤维细胞数量以及生存率之间的关系，确定CF对ALI/ARDS的最佳预测值，评价CF的预后价值，为临床探索发现一种新的ALI/ARDS预后指标。

Acute lung injury (ALI) and its extreme form, acute respiratory distress syndrome (ARDS) remain has high mortality, poor prognosis. Poor outcome of ALI/ARDS is correlates with excessive fibroproliferation . Circulating fibrocytes (CF)are a newly identified leukocyte subpopulation that come from bone marrow displaying fibroblast-like property, coexpressing CD45+Col-1+. Circulating fibrocytes rapidly enter sites of tissue injury, play an important role in fibroproliferative repair. We hypothesized that circulating fibrocytes are recruited at the site of lung injury and that their presence could be associated with a poor outcome. Our research include two parts.The first one is going to establish ALI mice models by intratracheal instillation of LPS. GFP transgenic mice bone marrow cells will be injected into ALI mice. CF engraftment in response to CXCL12/CXCR4 and differentiation in the lung of WT mice will be observed under confocal fluorescence microscope, CF and differentiated CF will be quantified by flow cytometry. Analyze the relationship of CF counts with ALI development,lung injury scores,survival rate.Clarifying that CF contribute to ALI fibroproliferation stage and poor prognosis.The second one is to choose ALI/ARDS patients to quantify fibrocytes in periblood and BALF, compare CF counts with disease progress,clinical parameters,mortality,evaluate the prognostic value of CF . The counts of circulating fibrocyte from patients with ALI /ARDS or without ALI/ARDS will be compared . A multivariate analysis using a Cox model will be performed to study CF be an independent predictors of survival.Receiver operating curve (ROC) will be used to identify a threshold value in patients with ALI/ARDS.The research may illuminate that CF are a novel reliable indicator of poor prognosis in ALI/ARDS.