Department of Rheumatology, Faculty of Medicine, Firat University, Elazig, Turkey.
Department of Internal Medicine, Eleskirt State Hospital, Agri, Turkey.
Int J Rheum Dis. 2021 Jun;24(6):795-802. doi: 10.1111/1756-185X.14114. Epub 2021 Apr 9.
Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is a monoclonal antibody against interleukin (IL)-17A. Metformin, a widely used antidiabetic medication, has anti-proliferative, immunomodulating and anti-fibrotic activities. The purpose of our study is to determine the therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced dermal fibrosis. Fifty Balb/c female mice were divided into 5 groups: (group 1 control, 2 sham, 3 secukinumab, 4 metformin and 5 secukinumab + metformin). The mice in the control group received 100 μL phosphate-buffered saline (PBS), while the mice in other groups received 100 μL (100 μg) BLM in PBS subcutaneously (sc) every day for 4 weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10 mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50 mg/kg/d for 28 days. All groups of mice were sacrificed at the end of the 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue messenger RNA (mRNA) expressions of IL-17 and collagen 3A were measured by real-time polymerase chain reaction. Repeated BLM injections had caused dermal fibrosis. In addition, the mRNA expressions of IL-17 and collagen 3A were increased in the BLM group. Secukinumab and metformin ameliorated dermal fibrosis. They decreased dermal thickness and tissue IL-17A and collagen 3A mRNA levels. Secukinumab and metformin exhibit anti-fibrotic effects in the BLM-induced dermal fibrosis.
虽然系统性硬化症的确切发病机制尚不清楚，但人们认为免疫激活在发病机制中起着突出的作用。司库奇尤单抗是一种针对白细胞介素（IL）-17A 的单克隆抗体。二甲双胍是一种广泛使用的抗糖尿病药物，具有抗增殖、免疫调节和抗纤维化作用。我们研究的目的是确定司库奇尤单抗和二甲双胍对博莱霉素（BLM）诱导的皮肤纤维化的治疗效果。将 50 只雌性 Balb/c 小鼠分为 5 组：（第 1 组对照，第 2 组假手术，第 3 组司库奇尤单抗，第 4 组二甲双胍，第 5 组司库奇尤单抗+二甲双胍）。对照组小鼠接受 100μL 磷酸盐缓冲盐水（PBS），而其他组小鼠每天接受 100μL（100μg）BLM 皮下（sc）注射，共 4 周。此外，第 3 组和第 5 组小鼠每周 sc 接受 10mg/kg 的司库奇尤单抗，第 4 组和第 5 组小鼠每天口服 50mg/kg 的二甲双胍共 28 天。第 4 周末，所有组小鼠均被处死并取组织样本进行分析。除了组织病理学分析外，还通过实时聚合酶链反应测量皮肤组织中白细胞介素 17（IL-17）和胶原蛋白 3A 的信使 RNA（mRNA）表达。反复 BLM 注射导致皮肤纤维化。此外，BLM 组的 IL-17 和胶原蛋白 3A 的 mRNA 表达增加。司库奇尤单抗和二甲双胍改善了皮肤纤维化。它们降低了皮肤厚度和组织中 IL-17A 和胶原蛋白 3A 的 mRNA 水平。司库奇尤单抗和二甲双胍在 BLM 诱导的皮肤纤维化中表现出抗纤维化作用。
