Shi Hai, Lu Rujian, Wang Shuo, Chen Honglin, Wang Fei, Liu Kun
Department of Cardiothoracic Surgery, The Third People's Hospital of Nantong, Nantong, Jiangsu, 226001, People's Republic of China.
Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
Inflammation. 2017 Jun;40(3):937-945. doi: 10.1007/s10753-017-0538-0.
Acute lung injury (ALI) is one of the most important complications after cardiopulmonary bypass (CPB) and the complex pathophysiology remains to be resolved incomplete. SDF-1/CXCR4 chemokine axis can chemotactically accumulate inflammatory cell to local tissue and regulate the release of inflammatory factors, and SDF-1 has a strong chemotaxis effect on neutrophils with CXCR4. Since CPB animal model was difficult to establish, there was still no report about the effect of SDF-1/CXCR4 on neutrophil chemotaxis in ALI after CPB. Here, a stable CPB rat model was constructed to clarify the role of SDF-1/CXCR4 axis in the CPB-induced ALI. Real-time quantitative PCR (RT-qPCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of SDF-1 and CXCR4 in lung tissues, blood, bronchoalveolar lavage (BALF), and/or isolated neutrophils. SDF-1/CXCR4 was increased after CPB, both of that were increased in blood; CXCR4 was increased in neutrophils; SDF-1/CXCR4 was also increased in BALF of CPB model. Results indicated that SDF-1/CXCR4 axis played a key role in the process of early ALI after CPB, also showed that lung injury was significantly reduce after blocking SDF-1/CXCR4 axis, suggest that CXCR4 might be a new target for ALI treatment.
急性肺损伤(ALI)是体外循环(CPB)后最重要的并发症之一,其复杂的病理生理学仍未完全解决。SDF-1/CXCR4趋化因子轴可趋化募集炎症细胞至局部组织并调节炎症因子的释放,且SDF-1对表达CXCR4的中性粒细胞具有很强的趋化作用。由于CPB动物模型难以建立,目前尚无关于SDF-1/CXCR4对CPB后ALI中性粒细胞趋化作用影响的报道。在此,构建稳定的CPB大鼠模型以阐明SDF-1/CXCR4轴在CPB诱导的ALI中的作用。采用实时定量PCR(RT-qPCR)、蛋白质免疫印迹分析和酶联免疫吸附测定(ELISA)检测肺组织、血液、支气管肺泡灌洗液(BALF)和/或分离的中性粒细胞中SDF-1和CXCR4的变化。CPB后SDF-1/CXCR4升高,二者在血液中均升高;CXCR4在中性粒细胞中升高;CPB模型的BALF中SDF-1/CXCR4也升高。结果表明,SDF-1/CXCR4轴在CPB后早期ALI过程中起关键作用,同时表明阻断SDF-1/CXCR4轴后肺损伤明显减轻,提示CXCR4可能是ALI治疗的新靶点。