多西他赛治疗大鼠类风湿关节炎模型的组织病理学评价

Omar Mustafa Alghulami, Ghaith A. Jasim, Suzan Yousif Jasim**
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引用次数: 0

摘要

类风湿关节炎是一种免疫介导的疾病,影响滑膜关节。滑膜组织、软骨、骨和较少出现的关节外结构依次经历炎症变化。紫杉醇的半合成等效物多西紫杉醇是一种抗肿瘤药物。甲氨蝶呤是早期RA的一种治疗方法,可能对肽基精氨酸脱亚胺酶4型荧光试验有轻微的负面影响。然而,由于耐药或副作用,30%的患者未能在第一年内完成治疗。类风湿性关节炎患者的滑膜浸润着表达肽基精氨酸脱亚胺酶4型的巨噬细胞和中性粒细胞,它们在类风湿性关节炎发病中的作用在于产生以抗环瓜氨酸肽抗体为靶点的瓜氨酸化新表位。本研究的目的是评估多西紫杉醇和甲氨蝶呤对关节结构的抗炎作用。方法:将40只雄性Wister大鼠分为5组,每组8只。大鼠皮下注射完全弗氏佐剂诱导病变。第一组是对照组,这是唯一一组(健康未经治疗的)大鼠。第二组给予完全的弗洛伊德辅助治疗。对照组和诱导组分别腹腔注射生理盐水0.5ml。在初步实验的基础上,第三组大鼠给予多西紫杉醇1 mg/kg/次腹腔注射。第四组腹腔注射甲氨蝶呤1 mg/kg/周。第五组患者同时给予甲氨蝶呤和多西他赛半剂量。测量关节炎指数,并对膝关节进行组织病理学检查。结果:多西他赛组关节炎指数明显降低(p≤0.05)。多西紫杉醇组和甲氨蝶呤组诱导大鼠关节炎的组织学评分(细胞增生、肉芽组织形成、白细胞浸润、软骨破坏、糜烂强度及关节软骨厚度)水平显著降低(p≤0.05)。结论:本研究显示多西他赛可能通过显著降低组织学评分而具有抗关节炎作用(p≤0.05)。
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Histopathological evaluation of docetaxel effects in treatment of rheumatoid arthritis induced in rat model
Rheumatoid arthritis is an immune-mediated condition that affects synovial joints. Synovial tissue, cartilage, bone, and less frequently extra-articular structures which in turn experience inflammatory changes. Paclitaxel's semi-synthetic equivalent, docetaxel, is an anti-neoplastic drug. Methotrexate is a treatment for early RA and may have a mildly negative impact on peptidyl arginine deiminase type 4 fluorescence test. However, 30% of patients fail to complete treatment within the first year due to resistance or side effects. The synovial membrane of Rheumatoid arthritis patient infiltrated with macrophages and neutrophils that express peptidyl arginine deiminase type 4 which their effect in rheumatoid arthritis pathogenesis lies in the generation of citrullinated neoepitopes that are Anti cyclic citrullinated peptide antibodies-targeted. The purpose of this study: was to assess the anti-inflammatory effects of docetaxel and methotrexate on the joint structure. Methods: Five groups of eight rats were formed from the 40 male Wister rats. Complete Freund’s adjuvant was injected subcutaneously into rats to induce the disease. The first group is control group which was the only group consists of (healthy untreated) rats. Second group was received complete Freund’s adjuvant. 0.5ml of ordinary saline was intraperitoneally administered to both the control and induction groups. Based on a preliminary experiment, the third group was given intraperitoneally 1 mg/kg/on alternative day docetaxel. The fourth group was given intraperitoneally 1 mg/kg/week of Methotrexate. Fifth group was given a half dose of both Methotrexate and docetaxel concurrently. Arthritis index was measured and Knee joint was histopathological examined. Results: significant Arthritis Index decrease in docetaxel group (p≤0.05). Significant lowering Histometric scoring (p≤0.05) in docetaxel, and Methotrexate group (cellular hyperplasia, formation of granulation tissue, infiltration of leukocytes, destroying of cartilage and intensity of erosion & Articular cartilage thickness) level in rats induced arthritis. Conclusion:  This study showed that docetaxel may have anti-arthritic effects through their significant lowering Histometric scoring(p≤0.05).
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