缓释LOX蛋白的纳米复合纤维在盆底筋膜组织修复中的作用及其机制的研究

利用聚丙烯网片的盆底重建手术易出现网片侵蚀这一严重并发症，而近年推出的可吸收生物网片，仍存在术后复发率过高的问题，因此，设计一种能降低网片侵蚀及术后复发风险的新型网片，是盆底重建领域的迫切需求。我们前期研究发现LOX能促进盆底筋膜中胶原蛋白的合成，提高筋膜中胶原含量，可能是通过调控MMPs的活性，促进了成纤维细胞胶原蛋白mRNA的表达。但LOX直接应用于盆底重建，尚存在盆底筋膜局部给药难、药物利用率低等问题，并且作用机制尚不完全明确。本项目，我们通过设计携载LOX的纳米复合纤维，利用可吸收纳米纤维作为网片支架，原位缓释LOX诱导筋膜再生，体外考察LOX促进成纤维细胞分泌胶原蛋白，体内分析LOX对筋膜修复的重要作用，进一步研究LOX是否通过TGF-β/Smad、MARK、AP1等信号通路调控MMPs/TIMPs活性以促进筋膜修复，明确LOX的作用机制，以期为盆底重建提供安全、有效的新型网片。

Accumulated controversies globally for the usage of polypropylene mesh in pelvic floor reconstruction due to the serious complication of mesh erosion. In order to reduce the risk of mesh erosion, absorbable bio-mesh was introduced in recent years, but with high rate of recurrence. There are urgent clinical needs to reduce the risk of recurrence and mesh erosion. Our previous study found that the LOX can upgrade the mRNA expression of fibroblast collagen, thus increasing the content of collagen in the fascia, which laid the basis for the construction of nanometer mesh with sustained releasing LOX for pelvic organ prolapse, whose mechanism, however, remains unclear. We hypothesized that sustained-releasing LOX may reduce expression of MMPs by the Smad, MARK and AP1 signal pathway, or upregulate the expression of TIMPs, leading to inactivation of MMPs, thus increasing the synthesis of collagen. In this study, we aimed to construct nano-composite fiber carrying LOX, with sustained releasing pattern. By employing the absorbable nano-fiber as the mesh scaffold, in situ releasing LOX is supposed to contribute to regeneration of fascia, which is to be assessed by the effects of LOX on fibroblasts collagen secretion in vitro and fascia regeneration in vivo, expecting to clarify the regulatory mechanism and provide a novel, safe and effective mesh for clinical usage.