成纤维细胞过度增殖和外基质沉积是膝关节内瘢痕粘连形成的重要因素，但具体的形成机制尚未完全明确。层粘连蛋白是一个重要的细胞外基质成分，而Wnt/β-catenin信号通路的异常激活可引起成纤维细胞增殖和纤维过度增生。前期研究发现瘢痕成纤维细胞中层粘连蛋白α表达明显升高；上调层粘连蛋白α能够促进Wnt和β-catenin表达。本研究拟进行：1、体外二维环境中培养人成纤维细胞，探讨层粘连蛋白α通过Wnt信号通路调控细胞增殖的作用和机制；2、体外制备脱细胞外基质三维培养基，探讨层粘连蛋白α在三维环境中通过Wnt信号通路调控人成纤维细胞增殖的作用和机制；3、建立兔膝关节内瘢痕粘连模型，探讨层粘连蛋白α调控成纤维细胞增殖、影响兔膝关节粘连的作用和机制。本研究使用三维培养微环境模拟体内的真实状态探讨层粘连蛋白α调控成纤维细胞增殖的机制，可阐明膝关节内粘连的形成机制，为瘢痕粘连的防治提供新线索和干预靶标。

Fibroblast excessive proliferation and external matrix deposition are important factors for the formation of intraarticular scar adhesion in the knee, but the definite mechanism is not yet fully clear. Laminin is one of the important extracellular matrix components, whereas abnormal activation of Wnt/β-catenin signaling pathway leads to the proliferation of fibroblasts and excessive fiber hyperplasia. Previous studies have shown that the expression of laminin α in scar fibroblasts significantly increased; up-regulation of laminin α could promote Wnt and β-catenin expression. In this study, we will aim to: (1) culture human fibroblasts in two-dimensional environment in vitro and explore the effect and mechanism of laminin α on regulating cell proliferation through the Wnt signaling pathway; (2) prepare the three-dimensional culture medium of decellularized extracellular matrix in vitro, and explore the effect and mechanism of laminin α on regulating proliferation of fibroblasts in three-dimensional environment through the Wnt signaling pathway; (3) establish the intraarticular scar adhesion model of knee joint in rabbit, and explore the effect and mechanism of laminin α on regulating fibroblasts proliferation and affecting the adhesion formation of knee. In this study, three-dimensional culture microenvironment is used to mimic the real internal state to explore the effect and mechanism of laminin α on regulating fibroblasts proliferation, which can clarify the formation of intraarticular adhesion of the knee and provide new clues and intervention targets for the prevention and treatment of scar adhesion.