纳米银-脱细胞基质通过SDF-1/VEGF通路介导的新生血管生成治疗肛瘘机制研究

肛瘘严重影响病人生活质量，治疗后容易复发和影响肛门功能。目前脱细胞基质（AEM）填塞治疗肛瘘，具有微创和保护肛门功能的特点，然而感染仍是肛瘘治疗失败的重要原因。本课题组一直围绕“肛瘘愈合机制”研究，我们前期研究发现：构建成功的纳米银-AEM材料，具有良好的生物安全性和抗菌性能，动物实验证实在治愈肛瘘同时，具有促进新生血管生成和抗炎作用。因此我们推测：纳米银-AEM一方面发挥纳米银的抑菌效能，重要的是通过改变微环境促进局部新生血管生成，促进肛瘘愈合。本研究拟利用纳米银-AEM填塞治疗肛瘘动物模型，聚焦新生血管生成，通过qRT-PCR等技术，研究EPC/SDF-1α/CXCR-4/VEGFR2血管生成信号通路在肛瘘愈合过程中的表达；进一步构建EPC-纳米银-AEM材料，明确EPC介导的新生血管生成对肛瘘组织愈合及下游信号通路的影响，旨在阐明纳米银-AEM通过促进新生血管生成促进肛瘘愈合的机制。

Anal fistula is usually caused by infection, easy to recur after surgery, usually impair anal function, and long-term non-healing might cause perianal cancer. At present, acellular matrix (AEM) has been used in the treatment of anal fistula with the characteristics of minimal invasion and anal protection. However, infection is still an important reason for the failure of minimally invasive treatment of anal fistula. Our research group has been focusing on "minimally invasive treatment and healing mechanism of anal fistula", and successfully constructed nano silver-AEM composite material in the early stage. Experiments in vitro have proved that nano silver-AEM has good biological safety and antibacterial properties, and animal experiments have confirmed that it can promote angiogenesis and have anti-inflammatory effects while curing anal fistula. We speculate that after nano-silver-AEM implantation, the antibacterial effect of nano silver can be exerted, and more importantly, local neovascularization can be promoted to facilitate anal fistula healing by changing the microenvironment. This study intends to use nano silver-AEM to treat anal fistula animal model, focusing on EPC/HIF-1α/SDF-1α/CXCR-4/VEGF-A/VEGFR2 angiogenic signaling pathway in the process of anal fistula healing by using immunohistochemistry, western blot, immunofluorescence staining, qRT-PCR techniques, and so on. We intend to further construct EPC-nano silver-AEM composite, illuminate EPC mediated angiogenesis during anal fistula healing and the influence on the downstream signaling pathways of EPC. The aim of this study is to elucidate the mechanism of nano silver-AEM promoting anal fistula healing by promoting neovascularization, and to provide a feasible theoretical basis for anal fistula treatment.