系统性硬化症是一种影响皮肤及多种内脏器官的多器官纤维化性疾病。尽管病变组织中异常激活的纤维母细胞是机体纤维化作用的主要靶点，但针对组织纤维化过程，目前尚未建立统一的治疗策略。近来研究证实，在不同疾病中细胞内环磷酸鸟苷水平的升高可增加纤维化水平。该研究目的在于评估体外培养的硬皮病患者纤维母细胞内环磷酸鸟苷的抗纤维化性能。磷酸二酯酶-5抑制剂西地那非能够以剂量依赖性的方式提高皮肤纤维母细胞内环磷酸鸟苷的水平。应用西地那非治疗能够显著减少多个促纤维化因子的表达，从而通过上调转化生长因子-β1(TGF-β1)达到治疗系统性硬化症皮肤成纤维化的目的。这些抑制作用通过非经典的 TGF-β信号转导通路起效。该研究发现西地那非可能是治疗系统性硬化症组织纤维化及血管病的一种新方法。

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        附原文：

Abstract：

        Systemic sclerosis(SSc) is a multi-organ fibrotic disease thataffects theskinand variousinternal organs. Therapeutic strategies for tissue fibrosis have not beenestablished; however, aberrantly activated fibroblasts in affectedlesionsare key targets for modulating fibrosis.Recently, increased intracellular cyclic GMP (cGMP) levels were demonstrated toimprove fibrosis levels in various diseases. The purpose of this study was toassess the anti-fibrotic properties of cGMP in cultured fibroblasts frompatients with SSc. The phosphodiesterase (PDE) 5 inhibitor sildenafil increasedthe intracellular cGMP levels inskinfibroblastsin a dose-dependent manner. Sildenafiltreatmentalso significantly decreased the expression ofseveral pro-fibrotic factors that were upregulated by TGF-β1treatmentin SScskinfibroblasts.These inhibitory effects occurred via non-canonical TGF-β signaling. Ourfindings revealed that sildenafil might be a novel strategy to treat tissuefibrosis and vasculopathy in SSc.

        引自：

        Higuchi T et al.Sildenafil attenuates the fibrotic phenotypeofskinfibroblasts in patients withsystemic sclerosis.Clin Immunol.2015 Dec;161(2):333-8. doi: 10.1016/j.clim.2015.09.010. Epub 2015 Sep 24.