pMSCs通过CXCL12/CXCR4轴调控巨噬细胞在急性肺损伤中的作用和机制研究

Acute lung injury (ALI), a severe lung syndrome with high morbidity and mortality, has become a critical challenge in the field of respiratory crisis. Evidence has shown that the progress of pulmonary inflammation is closely related to the phenotype and function of macrophage. Placenta mesenchymal stem cells (pMSCs) can regulate the macrophage differentiation from proinflammatory M1 type to anti-inflammatory M2 type. Our previous study has demonstrated that pMSCs can alleviate the inflammatory response induced by Lipopolysaccharide in RAW264.7 macrophage model. The current focus of the role of CXCL12/CXCR4 axis in ALI is mainly on neutrophils and epidermal cells. It has not been reported whether CXCL12/CXCR4 axis can alleviate inflammation and promote repair by regulating macrophages in ALI. Our study is to investigate the role of CXCL12/CXCR4 axis in the process of pMSCs regulating alveolar macrophages to M2 type differentiation by overexpressing or knocking down CXCL12, thereby providing a novel therapeutic perspective for ALI.

急性肺损伤（Acute lung injury, ALI）是发病率和死亡率均较高的一种严重肺部综合征，已成为当前呼吸危重症领域亟待解决的难题。文献报道肺部炎症的进展与巨噬细胞表型和功能密切相关，胚胎间充质干细胞（placenta Mesenchymal Stem Cells，pMSCs）能够调节巨噬细胞从促炎的M1型向抗炎的M2型分化。我们的前期研究结果显示pMSCs可以抑制脂多糖诱导的RAW264.7巨噬细胞炎症模型的炎症反应；目前有关CXCL12/CXCR4轴在ALI中作用主要集中于中性粒细胞和表皮细胞，而在ALI中CXCL12/CXCR4轴是否可以通过调节巨噬细胞而缓解炎症促进修复尚未见报道。我们拟通过在pMSCs中过表达和敲低CXCL12的表达探讨pMSCs通过CXCL12/CXCR4轴调控肺泡巨噬细胞向M2型分化进而起到治疗ALI的作用，为ALI的治疗提供新视角。

项目背景：急性肺损伤（Acute lung injury, ALI）是发病率和死亡率均较高的一种严重肺部综合征，已成为当前呼吸危重症领域亟待解决的难题。文献报道肺部炎症的进展与巨噬细胞表型和功能密切相关，胚胎间充质干细胞（placenta Mesenchymal Stem Cells，pMSCs）能够调节巨噬细胞从促炎的M1型向抗炎的M2型分化。.主要研究内容：分离鉴定出pMSCs；建立RAW264.7 细胞炎症模型，我们用qPCR检测炎症相关因子表达，发现炎症因子TNF-α在LPS组明显升高，用pMSC治疗的组显著下降，而抗炎因子IL-10的表现相反。用LPS建立动物模型，气管滴注pMSC，利用qPCR检测肺泡灌洗液BALF，LPS组蛋白明显增高，LPS+pMSC组下降；取肺组织切片，吉姆萨染色后，LPS+pMSC组炎症细胞显著减少, 表明向大鼠气管滴注pMSCs后的肺泡炎症显著减轻；细胞模型中，用WB检测CXCL12表达，动物模型中，取肺组织切片免疫组化染色，发现LPS组中的CXCL12表达显著高于LPS+pMSCs组，表明pMSCs能够通过调节CXCL12减轻肺部炎症。.主要科学意义：胚胎间充质干细胞可以有效缓解LPS诱导的小鼠急性肺损伤，并且其肺保护作用可能与CXCL12有关。