Gözel Nevzat, Çakirer Maşallah, Karataş Ahmet, Tuzcu Mehmet, Özdemir Fethi Ahmet, Dağli Adile Ferda, Şahin Kazım, Koca Süleyman Serdar
Department of Internal Medicine, Medical Faculty of Fırat University, Elazığ, Turkey.
Department of Rheumatology, Medical Faculty of Fırat University, Elazığ, Turkey.
Arch Rheumatol. 2017 Nov 27;33(3):309-315. doi: 10.5606/ArchRheumatol.2018.6652. eCollection 2018 Sep.
This study aims to examine the effects of sorafenib on a collagen-induced arthritis model.
The study included 50 randomly selected female Wistar-albino rats (8-10-week-old, weighing between 200 g to 250 g). The rats were divided into five equal groups as control, arthritis, etanercept, sorafenib high-dose, and sorafenib low-dose groups, respectively. Arthritis was induced by injecting mixed intradermal chicken type II collagen and incomplete Freund's adjuvant. Twenty-four hours after the advent of arthritis; rats in group 3 were injected subcutaneous etanercept (6 mg/kg/week), while those in groups 4 and 5 were given sorafenib (10 or 30 mg/ kg/day) orally until they were sacrificed on the 34th day. The rat claws and trunk bloods were carefully examined to note perisynovial inflammation and cartilage/bone injury through histopathology. Tissue vascular endothelial growth factor (VEGF) and VEGF receptor levels were carefully checked using western blot analysis.
Analysis of the experimental data showed that collagen-induced arthritis decreased in treatments groups after 12-13 days and 34th day in contrast with the arthritis group. Histopathological examination revealed broad perisynovial inflammation and cartilage/bone break down in the arthritis group. Compared to the control group, tissue VEGF and VEGF receptor levels increased in the arthritis group. Sorafenib and etanercept decreased tissue VEGF and VEGF receptor levels, perisynovial inflammation, damage of cartilage/bone.
Our findings indicate that sorafenib treatment ameliorates collagen-induced arthritis with anti-VEGF effectiveness.
本研究旨在探讨索拉非尼对胶原诱导性关节炎模型的影响。
本研究选取50只随机挑选的雌性Wistar白化大鼠(8 - 10周龄,体重200克至250克)。将大鼠分为五组,每组数量相等,分别为对照组、关节炎组、依那西普组、索拉非尼高剂量组和索拉非尼低剂量组。通过皮内注射混合的鸡II型胶原和不完全弗氏佐剂诱导关节炎。关节炎出现24小时后;第3组大鼠皮下注射依那西普(6毫克/千克/周),而第4组和第5组大鼠口服索拉非尼(10或30毫克/千克/天),直至在第34天处死。仔细检查大鼠爪子和躯干血液,通过组织病理学观察滑膜周围炎症和软骨/骨损伤情况。使用蛋白质印迹分析仔细检测组织血管内皮生长因子(VEGF)和VEGF受体水平。
实验数据分析表明,与关节炎组相比,治疗组在第12 - 13天和第34天时胶原诱导性关节炎有所减轻。组织病理学检查显示关节炎组存在广泛的滑膜周围炎症和软骨/骨破坏。与对照组相比,关节炎组组织VEGF和VEGF受体水平升高。索拉非尼和依那西普降低了组织VEGF和VEGF受体水平、滑膜周围炎症以及软骨/骨损伤。
我们的研究结果表明,索拉非尼治疗通过抗VEGF作用改善了胶原诱导性关节炎。