骨髓间充质干细胞对大鼠光气吸入性肺损伤的保护作用及Wnt/β-catenin信号通路对其调控机制的研究

Chemical inhalation-induced lung injury is a common disease in the field of critical illness, there is no specific therape in the clinical and the mortality rate is high,their pathophysiological mechanisms is similar.Studies have shown that bone mesenchymal stem cells (MSCs) can reduce lung injury , the repair of the lung air-blood barriers and the regulation of inflammatory responses both play an important role, Wnt/β-catenin signaling pathway may be involved in regulation of these two processes, but the mechanism remains obscure. our previous experiments suggest that the quantity of protein expression of Wnt1, Wnt3a, β-catenin change before and after the intervention of MSCs in lung injury, to further confirm the role of MSCs and Wnt/β-catenin signaling pathway in inhalation lung injury and their mutual adjustment mechanism. The experimental use the phosgene inhalation lung injury on rats as a model, by molecular biological techniques, recombinant adenovirus vector and stem cell transplants and other means, the change of lung air-blood barrier, inflammatory factors, the components of the Wnt/β-catenin signaling pathway will be measured before and after the intervention of MSCs, to clear the protective effect of MSCs in phosgene-induced lung injury on rats, and the regulated role of Wnt/β-caten signaling pathway in this mechanism, the results are expected to provide a theoretical and experimental basis for the treatment of MSCs on chemical-induced lung injury.

化学源吸入性肺损伤是常见急危重症，临床无特效治疗，死亡率高，其病理生理过程有相似性。研究表明，骨髓间充质干细胞（MSCs）通过修复肺气血屏障及调节炎症反应两方面保护肺损伤，Wnt/β-catenin信号通路可能参与其中，具体机制不清。我们前期实验提示：MSCs干预肺损伤大鼠模型前后肺组织Wnt1，Wnt3a，β-catenin蛋白表达量变化，初步证实Wnt/β-catenin信号通路参与MSCs对肺损伤的保护作用及两者的调控。本研究采用光气吸入性肺损伤大鼠模型，应用MSCs干预，通过分子生物学技术、重组腺病毒载体构建和干细胞携载基因等手段，检测MSCs干预前后肺气血屏障、炎症因子、Wnt/β-catenin信号通路各组分的变化，以期阐明MSCs对大鼠光气吸入性肺损伤的干预及Wnt/β-catenin信号通路在其中的调控作用，可望为MSCs干预化学源性肺损伤提供理论基础，为临床治疗寻找方法。

化学源吸入性肺损伤是常见急危重病，临床上无特效治疗，死亡率高，我们的研究致力于光气吸入性肺损伤的干预治疗，以提高化学源性肺损伤的治疗水平。研究提示骨髓间充质干细胞（MSCs）通过修复肺气血屏障及调节炎症反应两方面发挥保护光气吸入性肺损伤的作用，Wnt/β-catenin信号通路在其中发挥重要的调节作用。同时开展其他相关的干预治疗，如应用干细胞携载基因，进一步加强了MSCs的治疗作用。为MSCs干预化学源性肺损伤的临床转化提供了依据。