间充质干细胞通过KGF-2/PI3k/Akt/NF-κB调控Th17/Treg平衡促进肺损伤修复的机制研究

动物急性肺损伤（ALI）和人急性呼吸窘迫综合征（ARDS）是以呼吸窘迫和顽固性低氧为主要表现，除了通过小潮气量机械通气降低病死率外，尚无其他有效的药物治疗措施，病死率仍然较高。我们前期研究发现间充干细胞（MSC）可以通过旁分泌KGF-2改善急性肺损伤，但其机制未明。我们预实验结果表明ARDS时存在Th17/Treg失衡：Treg/Th17细胞比例下降；MSC和KGF-2能够纠正Treg/Th17细胞比例的下降。因此，我们推测MSC通过KGF-2/PI3K/Akt/NF-κB信号通路调控Th17/Treg平衡，并进一步抑制肺损伤。本研究拟在ARDS患者临床标本中检测Treg细胞和Th17细胞时程变化；动物和细胞实验探索MSC和KGF-2对Th17/Treg平衡的影响及机制。本研究结果预期为ARDS的治疗和防治奠定理论基础。

Acute lung injury (ALI) of animal and acute respiratory distress syndrome (ARDS) of human are characterized by respiratory distress and refractory hypoxemic respiratory failure. However, current management is mainly supportive such as small tidal volume mechanical ventilation, but mortality still remains high. Our previous studies found that mesenchymal stem cells (MSC) alleviated ALI by secretion of KGF-2, but the mechanism remians unclear. Our preliminary experimental results indicated the imbalance of Tregs and Th17 cells existed in ALI; MSC and KGF-2 could up-regulated the ratio of Tregs and Th17 cells. Thus, we speculated that mesenchymal stem cells regulate the balance of Th17 and regulatory T cells via KGF-2/PI3k/Akt/NF-κB signaling pathway in acute lung injury. The current study will test the ratio of Treg and Th17 cells in ARDS patient; and clarify the mechanism of MSC regulating the number and function Tregs and Th17 cells in ALI animal model and cell level. The resulats would offer new treatment for ARDS.