西来昔布对佐剂性关节炎大鼠模型的抗炎消肿作用观察

Studies on anti-infl ammatory effects and immune modulating functions of xelecoxib

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 investigate the anti-inflammatory activity and immune modulating function of xelecoxib in animals. Methods Animal models for experimental inflammation including primary adjuvant arthritis （experiment 1） and secondary adjuvant arthritis （experiment 2 and 3，investigate the prevention and treatment of xelecoxib respectively） were adopted to validate the effect of xelecoxib. Besides, the influence of drugs on lymphocyte proliferation was determined. 208 male SD rats and 30 female C57BL/6 mice were divided into normal, model, positive groups （celecoxib 10 mg/kg and indometacin 2.5 mg/kg） and xelecoxib groups （1.25、2.5、5 and 10 mg/kg） in the experiment. Results Experiment 1 showed that the xelecoxib （10 mg/kg） significantly reduced swelling volume in 18 h after induced inflammation compared with model group （P 〈 0.05）. In experiment 2, xelecoxib（5 and 10 mg/kg） decreased swelling side volume in 9, 12, 15d after induced inflammation（P 〈 0.05 or P 〈 0.01）. Xelecoxib （2.5 mg/kg）showed similar results in 15 d after induced inflammation （P 〈 0.05 or P 〈 0.01）. The results of experiment 3 were that xelecoxib （1.25 mg/kg） and xelecoxib （2.5, 5 and 10 mg/kg） had the same effect on the swelling side in 25/27 d and 23/25/27 d after induced inflammation respectively （P 〈 0.05 or P 〈 0.01）. Moreover, it could reduce rats thymus index and spleen index to make the immune organ weight back to normal. The effect of xelecoxib （5 and 10 mg/kg） on inflammation and immune regulation was similar to celecoxib and indomethacin. Histopathological changes showed that it could relieve foot joint cartilage destruction and tissue inflammation and could inhibit lymph cell proliferation. Conclusion Xelecoxib has suppressive effect on inflammation and immune function.