基于KGF/KGFR介导角质形成细胞修复探讨验方“芪银三两三”治疗EGFR-TKI所致皮疹的效应机制研究

表皮生长因子受体酪氨酸酶抑制剂（EGFR-TKI）如吉非替尼，是晚期非小细胞肺癌的一线用药，其皮疹等不良反应与抗癌作用正相关。由于缺乏有效治疗药物，皮疹严重患者常被迫停药而贻误病情。前期临床观察发现，中医验方“芪银三两三”可以有效改善吉非替尼导致的皮疹；动物实验发现，该方可改善皮肤脱屑、减少炎症浸润和抑制角化层的异常增厚。这些研究表明，该方可作用于角质形成细胞，调节增殖与分化，但机制尚不明确。文献调研发现，该方有效组分黄芪可调节角化细胞生长因子（KGF），使其与KGFR结合，促进TGF-a表达，进一步激活EGFR通路；KGF/KGFR具有肺损伤保护作用，且不影响肿瘤的发生。因此提出假说：由KGF/KGFR-TGF-a-EGFR介导的角质形成细胞增殖与分化通路，可能是中医药治疗EGFR-TKI皮疹的重要作用机制。本研究将通过体内、外实验，探讨该通路损伤修复机制，为临床联合用药提供实验依据。

Epidermal growth factor receptor tyrosinase inhibitor (EGFR-TKI), such as  gefitinib, is a first-line treatment for advanced non-small cell lung cancer, but the adverse reactions represented by rash are positively correlated with anticancer effects. Because of the lack of effective treatment for rash drugs, patients with severe rashes are forced to stop the drug and delay the disease. Previous clinical observations found that the traditional Chinese medicine prescription "Qi Yin San Liang San" can effectively improve the rash caused by gefitinib. Animal experiments found that "Qi Yin San Liang San" can effectively improve skin desquamation, reduce inflammatory infiltration and inhibit the abnormal increase of keratinized layer thick. These studies suggest that "Qi Yin San Liang San" can act on keratinocytes to regulate proliferation and differentiation, but the mechanism remains unclear. Literature investigation found that the effective component of Astragalus membranaceus can regulate keratinocyte growth factor (KGF), KGF/KGFR promote TGF-a expression, and further activate EGFR pathway; KGF/KGFR has lung injury protection without affecting The occurrence of tumors.  Therefore, we hypothesized that keratinocyte proliferation and differentiation pathway mediated by KGF/KGFR-TGF-a-EGFR may be an important mechanism of action for the treatment of rash. In order to clarify this scientific problem, this experiment will use KGFR inhibitors to explore the mechanism of KGF/KGFR-TGF-a-EGFR skin damage repair both in vivo and in vitro assay, and provide experimental evidence for clinical combination.