仿生腱鞘膜调控巨噬细胞经典活化防治肌腱粘连的机制及干预研究

Anti-adhesion membranes made by biomaterials have been widely used for peritendinous anti-adhesion, but they can only act as physical barriers and usually lead to inflammation with poor outcome. In our previous study, biomimetic sheath anti-adhesion membrane was fabricated to promote tendon healing and sliding, but it still leads to inflammation. We further revealed that inflammation caused by biomaterial membranes has a close relationship with macrophages (Mφ) and pro-inflammatory factors and confirmed that nuclear factor KappaB (NF-κB) activated by biomaterials can induce the secretion of inflammatory factors from Mφ. According to our previous study, as the source of inflammatory factors, Mφ can be classically activated (M1) by NF-κB in Mφ NF-κB transgenic mice. Therefore, we assume that the anti-adhesion membranes made by biomaterials can lead to inflammation and poor anti-adhesion effect by activation of NF-κB to promote M1 Mφ to secrete inflammatory factors and that the membrane loaded with NF-κB inhibitor (PDTC) can inhibit inflammation and thus improve function. To verify this hypothesis, this project intends to prepare biomimetic sheath membranes using various polyester polymers and to reveal the influence of such membranes on Mφ and associated mechanism by investigating the expression of NF-κB, M1 type marks and inflammatory factors. Furthermore, the anti-adhesion effect and the mechanism will be examined through the Achilles tendon adhesion in transgenic mice model. Furthermore, anti-adhesion effect and its mechanism of the PDTC-loaded membrane will also be investigated to provide a new treatment and theoretical basis for peritendinous anti-adhesion.

生物材料所制防粘连膜已广泛用于防治肌腱粘连，但作用单一、易引发炎症，疗效不佳。我们前期构建了促进肌腱愈合和滑动的仿生腱鞘防粘连膜，但仍引发炎症；进一步发现该类膜引发的炎症与巨噬细胞（Mφ）及炎性因子密切相关；还证实生物材料能通过激活核因子-κB（NF-κB）促进Mφ分泌炎性因子；并利用Mφ特异性NF-κB转基因小鼠证实NF-κB通过调控Mφ经典活化（M1）介导炎性因子分泌。因此，我们假设该类膜通过激活NF-κB促进Mφ经典活化并分泌炎性因子，从而引发炎症、降低防粘连疗效；膜内负载NF-κB抑制剂（PDTC）可抑制炎症、提高疗效。为验证该假说，本课题拟采用多种聚酯类高分子构建仿生腱鞘膜，观察该类膜对Mφ增殖的影响，检测NF-κB、M1型标志物及炎性因子表达从而探讨机制；并利用上述小鼠构建跟腱粘连模型，考察该类膜的体内疗效及机制；还明确载PDTC膜的作用，为防治肌腱粘连提供新的方法和理论依据。

生物材料所制防粘连膜已广泛用于防治肌腱粘连，但作用单一、易引发炎症，疗效不佳。我们前期构建了促进肌腱愈合和滑动的仿生腱鞘防粘连膜，但仍引发炎症；进一步发现该类膜引发的炎症与巨噬细胞（Mφ）及炎性因子密切相关；还证实生物材料能通过激活核因子-κB（NF-κB）促进Mφ分泌炎性因子；并利用Mφ特异性NF-κB转基因小鼠证实NF-κB通过调控Mφ经典活化（M1）介导炎性因子分泌。因此，我们假设该类膜通过激活NF-κB促进Mφ经典活化并分泌炎性因子，从而引发炎症、降低防粘连疗效；膜内负载NF-κB抑制剂（JSH-23）可抑制炎症、提高疗效。为验证该假说，本课题拟采用多种聚酯类高分子构建仿生腱鞘膜，观察该类膜对Mφ增殖的影响，检测NF-κB、M1型标志物及炎性因子表达从而探讨机制；并利用上述小鼠构建跟腱粘连模型，考察该类膜的体内疗效及机制；还明确载JSH-23膜的作用，为防治肌腱粘连提供新的方法和理论依据。