伊马替尼在系统性硬化症的应用前景

摘要

系统性硬化症(systemic sclerosis,SSc)以胶原过度产生和细胞外基质过度沉积导致组织纤维化为主要特征.血小板源性生长因子受体(platelet-derived growth factor receptor,PDGFR)、转化生长因子-β(transforming growth factor-β,TGF-β)以及细胞免疫的异常可能参与了这一过程.甲磺酸伊马替尼(imatinib mesylate,IM)是一种人工合成的酪氨酸蛋白激酶抑制剂,最早被用于治疗慢性粒细胞白血病,近年发现其具有抗纤维化作用.目前认为,IM可以通过抑制PDGFR和TGF-β,并可能通过影响调节性T细胞的增殖和功能达到治疗SSc的目的.但是,IM治疗SSc的临床研究刚刚起步,其疗效及安全性有待已经启动的大规模随机对照临床试验(RCT)的结果来评价.%Systemic sclerosis is a multisystem fibrotic disorder characterized by excessive deposition of collagen and other extracellular matrix components. The disorders of platelet-derived growth factor receptor (PDGFR),transforming growth factor-β (TGF-β) and cell-mediated immunity are hypothesized to be involved in the pathogenesis of systemic sclerosis (SSc). Imatinib mesylate is a small molecule that antagonizes specific tyrosine kinases which has been approved to be the treatment of chronic myeloid leukemia. Recently,imatinib began to be used to treat SSc which is mostly based on the known anti-proliferative properties, as an inhibitor of PDGFR and TGF-β, even anti-regulatory T lymphocytes (Treg). The preliminary clinical data raised the possibility that patients with SSc may benefit clinically from imatinib therapy. Large prospective randomized clinical trials are needed to further investigate the effects of imatinib on SSc.Gratifyingly, several clinical trials using imatinib in SSc are currently in progress.