Abstract：
Peritendinous adhesion is a major cause of limb dysfunction and disability in clinical practice. Numerous studies suggest that activation of nuclear factor-κB (NF-κB) pathway in macrophages could be the pivotal figure in excessive collagen synthesis and thus peritendinous adhesion formation. In this study, we assumed this pathological process could be suppressed by inhibiting NF-κB phosphorylation and nuclear translocation using pyrrolidine dithiocarbamate (PDTC), a specific NF-κB inhibitor with the ability to penetrate cell membranes, in macrophages. Then, we conducted electrospinning process to incorporate PDTC into poly(L-lactic) acid (PLA) electrospinning membranes, that is, the PDTC-PLA membranes. Further, with integral film quality and stable drug release property, the PDTC-PLA membranes were subsequently analyzed in the capability and mechanism of preventing adhesion formation both in vitro and in vivo. Our results showed inhibition of macrophage proliferation as well as NF-κB pathway activation from in vitro assays and outstanding promotion in inhibiting NF-κB p65 phosphorylation and reducing adhesion formation from in vivo assays of PDTC-PLA compared to PLA membranes. In conclusion, our findings suggested that PDTC-PLA as an alternative therapeutic approach alleviated inflammation and peritendinous adhesion formation through NF-κB signaling pathway. STATEMENT OF SIGNIFICANCE: Pyrrolidine dithiocarbamate (PDTC) can be blended into poly-L-lactic acid (PLA) fibrous membranes by electrospinning process. This incorporation of PDTC into PLA is an effective way to inhibit proinflammatory activation of macrophages and to achieve advanced anti-adhesion outcome after tendon repair.
摘要：
在临床实践中，肌腱周围粘连是肢体功能障碍和残疾的主要原因。大量研究表明，巨噬细胞中核因子-κB（NF-κB）途径的激活可能是过度胶原蛋白合成并因此形成外周粘附的关键人物。在这项研究中,我们假设这一病理过程可以通过使用吡咯烷二硫代氨基甲酸酯（PDTC）抑制NF-κB磷酸化和核易位来抑制，一种具有穿透细胞膜能力的特异性NF-κB抑制剂，在巨噬细胞中。然后，我们进行了静电纺丝工艺，将PDTC掺入到聚（L-乳酸）（PLA）静电纺丝膜中，也就是说,PDTC-PLA膜。Further,具有整体膜质量和稳定的药物释放性能，随后分析了PDTC-PLA膜在体外和体内防止粘连形成的能力和机制。我们的结果表明，与PLA膜相比，体外测定抑制巨噬细胞增殖以及NF-κB途径激活，并在抑制NF-κBp65磷酸化和减少PDTC-PLA体内测定中粘附形成方面发挥突出作用。总之,我们的研究结果表明,PDTC-PLA作为一种替代治疗方法,可通过NF-κB信号通路缓解炎症和肌腱周粘连形成.重要声明:吡咯烷二硫代氨基甲酸酯(PDTC)可以通过静电纺丝工艺共混到聚-L-乳酸(PLA)纤维膜中。这种将PDTC掺入PLA是抑制巨噬细胞促炎活化和在肌腱修复后实现高级抗粘连结果的有效方法。
