清胰汤干预MSCs在体内归巢与分化治疗胰源性肺损伤的机制研究

Acute lung injury (ALI) is the leading cause of death in early severe acute pancreatitis (SAP). Treatment with Mesenchymal stem cells (MSCs) has opened up a new avenues for the disease by cellular repair and immunomodulation, but it is unable to reach a satisfactory therapeutic potential because of the low homing and differentiation rate in damaged lung. In this study, we investigate mechanisms of regulation of SDF-1 / CXCR4 and Wnt / beta-catenin signaling pathway in MSCs homing and differentiation, explore Qingyitang's interventionist targets and protective mechanism on MSCs survival, establish a safe, effective and easy way to regulate and promote MSCs migration to target tissue and enhance their directed differentiation rate using traditional Chinese medicine as a new intervening factors, thereby achieving the purpose of effective repair and reconstruct damaged lungs, reduce mortality and improve prognosis. By analyzing the correlation between transplant way, time and MSCs fate as well as theraputic effeciency, we'll filter out the optimized treatment program and oped up the new ways and ideas to the treatment of such kind of serious and refractory diseases, also lay foundation for application of Chinese medicine in the field of stem cells and regenerative medicine.

急性肺损伤 (ALI) 是重症急性胰腺炎 (SAP)早期死亡的主要原因，间充质干细胞（MSCs）因具有细胞修复与免疫调节作用而为此病的治疗开辟了新途径，但其在损伤肺组织内的归巢与分化率很低，无法达到满意的治疗效果。本研究通过揭示SDF-1/CXCR4和Wnt/β-catenin信号通路对MSCs归巢迁移与定向分化的调控机制，探索清胰汤对以上通路的干预靶点及对MSCs定植存活的保护作用与机制，建立以安全有效、易于推广的中药作为全新的干预因素，调控并促进MSCs向靶组织迁移、提高其定向分化率的新策略，从而达到有效修复重建损伤肺组织的结构与功能、降低死亡率并改善预后的目的；通过分析不同移植时期与途径对MSCs体内命运的影响及与治疗效果的相关性，筛选出最优化治疗方案，为中西医结合治疗此类重大难治疾病开辟新的思路与途径，也为中医药在干细胞与再生医学领域的应用奠定基础。

急性肺损伤（ALI）是重症急性胰腺炎（SAP）早期死亡的主要原因，间充质干细胞（MSCs）因具有细胞修复与免疫调节作用而为此病的治疗开辟了新途径。为解决在损伤肺组织内的归巢与分化率很低的问题，本研究构建了CXCR4质粒转染MSCs，使其过度表达CXCR4；在SDF-1作用下，明显提高体内、体外MSCs归巢效率；MSCs可以分化成肺泡上皮Ⅰ、Ⅱ型细胞，调节Wnt/β-catenin 信号通路可以对MSCs 分化可以进行有效调控，给予氯化锂干预Wnt/β-catenin 信号通路，可以明显提高MSCs 分化效率。清胰汤剂中的部分补益、抗氧化单味药物，促进MSCs 通过Wnt/β-catenin 信号通路分化成肺泡上皮Ⅰ、Ⅱ型细胞，从而达到有效修复、重建损伤肺组织的结构与功能。清胰汤联合MSCs治疗胰源性胰腺炎，可以明显提高治疗效果与效率，降低死亡率并改善预后。在给予清胰汤灌胃，降低机体内的炎症反应，能够保护MSCs，使MSCs充分发挥功能，促进治疗效果。该研究证明中西医集合能够功能互补，充分发挥效应。清胰汤单味药物能够促进MSCs分化，MSCs能够补充清胰汤组织修复功能。该研究为中西医结合治疗此类重大难治疾病开辟新的思路与参考，为中医药在干细胞与再生医学领域的应用奠定基础。