基于MCP-1/CCR2轴探讨大黄联合UC-MSCs移植治疗重症急性胰腺炎的机制研究

重症急性胰腺炎发病凶险，预后差，病死率高达10%-30%，属中医“腹痛”、“结胸”、“阳明腑实证”等范畴，运用中药大黄治疗有一定功效。脐带间充质干细胞移植可以减轻胰腺炎病情，改善预后，但仍然存在移植细胞存活率低、缺乏靶向性等问题。本课题拟通过中西医结合的手段，研究中药大黄联合脐带间充质干细胞移植治疗重症急性胰腺炎的疗效以及大黄对脐带间充质干细胞迁移及CCR2受体表达的影响，通过RNA干扰、Transwell细胞迁移以及激光共聚焦等方法，阐明MCP-1/CCR2通路在促进脐带间充质干细胞迁移以及治疗重症急性胰腺炎中的作用。本课题的完成有望提高脐带间充质干细胞移植效率和疗效，加速其在重症急性胰腺炎中的临床应用。同时在研究过程中，亦可对大黄改善损伤组织微环境，促进脐带间充质干细胞迁移与分化有新的发现，对于阐释大黄联合脐带间充质干细胞治疗重症急性胰腺炎的作用机理也具有十分重要的理论和临床意义。

Severe acute panereatitis (SAP) is a clinical acute abdomen,The mortality rate of SAP is about10%-30%, and the prognosis is unfevorable. Traditional chinese medicine consider SAP as “abdominal pain” “thoracic stagnation” “Yang Ming Fu-Organ Syndrome”. So far, inhibition of pancreatic exocrine, prophylactic antibiotic and nutrition supports are predominat therapy principals for SAP. Rhubarb play in the adjuvant treatment of SAP. Umbilical cord mesenchymal stem cells (UC‑MSCs) have been suggested as a candidate for SAP clinical applications, however, there are major limitations include the lack of organ‑specific accumulation and low survival rates of transplanted cells. In the present study, it was hypothesized that the rhubarb may enhance stem cell‑based tissue repair and regeneration by promoting the specific homing of UC-MSCs and the overall ability to drive them to the damaged area by MCP‑1/CCR2 axes. Therapeutic effects of Rhubarb combined with UC-MSCs transplantation on severe acute pancreatitis was analyzed using RNAi and confocal laser scanning microscope techniques. Subsequently, UC‑MSC were labeled with PKH26 and analyze migration，planting and differentiation. The expression levels of CCR2 were determined in the UC‑MSCs using RT-PCR and flow cytometry. The results of the present study may develop new protocols for the improvement of SAP therapy.