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目的观察非甾体类抗炎药物西来昔布的抗炎消肿作用和对免疫功能的影响。方法选取208只雄性SD大鼠进行以下试验:评价药物对大鼠佐剂性关节炎原发性病变的预防作用(试验1),试验1中大鼠随机分为模型组、阳性对照组(塞来昔布10 mg/kg)和西来昔布各剂量组(1.25、2.5、5和10 mg/kg)(n=8);评价药物对大鼠佐剂性关节炎继发性病变的预防作用(试验2)和治疗作用(试验3),试验2和试验3将SD大鼠随机各分为正常组、模型组、阳性对照组(塞来昔布10 mg/kg和吲哚美辛2.5 mg/kg)和西来昔布各剂量组(1.25、2.5、5和10 mg/kg)(n=10);除正常组外其他各组采用弗氏完全佐剂诱导关节炎。另选取30只雌性C57BL/6小鼠,用于观察药物对小鼠脾淋巴细胞转化反应的影响,随机分为空白对照组、阳性对照组(塞来昔布10 mg/kg)和西来昔布组(2.5、5和10 mg/kg)(n=6)。结果与模型组比较:试验1结果显示,西来昔布高剂量组(10 mg/kg)致炎后18 h的肿胀体积显著降低,差异具有统计学意义(P<0.05);试验2结果显示,西来昔布5 mg/kg和10 mg/kg剂量组致炎后9、12、15 d以及2.5 mg/kg剂量组致炎后15 d后的致炎侧肿胀体积显著降低,差异均有统计学意义(P<0.05或P<0.01);试验3结果显示,西来昔布1.25 mg/kg剂量组致炎后25和27 d,以及2.5、5和10 mg/kg剂量组致炎后23、25和27 d的致炎侧肿胀体积均显著减小,差异均有统计学意义(P<0.05或P<0.01)。西来昔布可改善大鼠胸腺指数和脾脏指数,恢复受试动物的免疫器官重量。西来昔布5和10 mg/kg剂量组在抗炎消肿、免疫调节方面,与阳性药塞来昔布和吲哚美辛作用比较差异无统计学意义。组织病理学变化显示,西来昔布可减轻足关节软骨破坏和软组织炎症,抑制小鼠脾淋巴细胞的转化。结论西来昔布具有抗炎消肿及免疫抑制作用。
Objective To observe the anti-inflammatory and non-swelling effect of non-steroidal anti-inflammatory drug celecoxib and its influence on immune function. Methods A total of 208 male Sprague-Dawley rats were selected to evaluate the prophylactic effect of drugs on the primary lesions of adjuvant arthritis in rats (Experiment 1). The rats in Experiment 1 were randomly divided into model group, positive control group Cocoxib 10 mg / kg) and celecoxib (1.25, 2.5, 5 and 10 mg / kg) (n = 8); evaluation of prophylaxis of adjuvant-induced secondary disease in rats (Experiment 2) and the therapeutic effect (experiment 3). In Experiment 2 and Experiment 3, SD rats were randomly divided into normal group, model group and positive control group (celecoxib 10 mg / kg and indomethacin 2.5 mg / kg) and celecoxib (1.25, 2.5, 5 and 10 mg / kg) (n = 10). All groups except the normal group were given complete Freund’s adjuvant to induce arthritis. Another 30 female C57BL / 6 mice were selected to observe the effects of the drugs on the splenic lymphocyte transformation in mice. They were randomly divided into blank control group, positive control group (celecoxib 10 mg / kg) Clot group (2.5, 5 and 10 mg / kg) (n = 6). Results Compared with the model group, the results of Experiment 1 showed that the volume of swelling in the high-dose celecoxib group (10 mg / kg) at 18 h after injection decreased significantly (P <0.05), and the result of Experiment 2 , The volume of proinflammatory swelling in the groups of 5 mg / kg and 10 mg / kg celecoxib at 9, 12, 15 d and 2.5 mg / kg were significantly decreased after 15 d Statistical significance (P <0.05 or P <0.01) .Experiment 3 showed that celecoxib 1.25 mg / kg at 25 and 27 days and 2.5, 5 and 10 mg / The volume of proinflammatory swelling at 23, 25 and 27 d were significantly decreased, with statistical significance (P <0.05 or P <0.01). Celecoxib improved the thymus index and spleen index in rats and restored the weight of the immune organs in the test animals. Celecoxib 5 and 10 mg / kg dose group in the anti-inflammatory swelling, immune regulation, and the positive drug celecoxib and indomethacin no significant difference in the role. Histopathological changes show that celecoxib can reduce foot cartilage destruction and soft tissue inflammation, inhibition of mouse spleen lymphocyte transformation. Conclusion Celecoxib has anti-inflammatory and immunosuppressive effects.