纤维化是系统性硬化病(SSc)的典型病理特征，与SSc 预后和死亡率密切相关。Wnt/β-catenin信号通路在SSc 纤维化过程中起着重要作用，是治疗SSc纤维化的关键靶点。前期研究表明，基于"肺脾肾-皮毛相关理论"组方中药--温阳化浊通络方治疗SSc临床效果显著，并能干预SSc皮损成纤维细胞生长周期而抑制其增殖，降低胶原、TGF-β1表达水平。本研究拟从温阳化浊通络方调控Wnt/β-catenin信号通路的角度出发，在体外皮肤成纤维细胞水平和SSc小鼠模型的整体水平上考察温阳化浊通络方对成纤维细胞表型转化、迁移、凋亡、ECM合成等的影响，以及对Wnt/β-catenin信号通路关键分子及靶基因表达的影响，明确其干预Wnt/β-catenin信号的作用环节和靶点，综合探讨温阳化浊通络方调控Wnt/β-catenin信号通路而发挥抗纤维化的作用机制，为SSc的防治提供科学依据。

Fibrosis is typical pathologic character of systemic sclerosis (SSc), which is related to prognosis and mortality of SSc. Wnt/β-catenin singaling pathway plays a vital role in SSc fibrosis and is important target in treating SSc fibrosis. Previous study indicated that Wenyang Huazhuo Tongluo Recipe (WYHZTLR) based on lung, spleen and kidney-skin correlation theory treated effectively SSc patients. WYHZTLR could intervene in the cell cycle of dermal fibroblasts from SSc lesion to inhibit the proliferation of dermal fibroblasts, and abated expression levels of collagen and TGF-β1 in vitro. The study on regulation of WYHZTLR on Wnt/β-catenin singaling pathway will be carried out. At the dermal fibroblast level and animal model of SSc level we will study the effects of WYHZTLR on phenotypic transformation, migration, apoptosis，ECM synthesis in fibroblasts and key molecule and target gene of Wnt/β-catenin singaling pathway. We will elucidate the action segment and target of WYHZTLR regulating Wnt/β-catenin singaling pathway. In this program, the mechanisms of WYHZTLR intervening in Wnt/β-catenin singaling pathway will be investigated systemically. The results will provide scientific basis for treatment of SSc.