塞来昔布联合莫西沙星对肺炎克雷伯杆菌肺炎大鼠肺部炎症标志物及组织病理学的影响

Effect of celecoxib combined with moxifloxacin on inflammatory markers and histopathology in rats with Klebsiella pneumonia

目的研究特异性环氧化酶-2(COX-2)抑制剂塞来昔布联合莫西沙星对肺炎克雷伯杆菌肺炎大鼠肺部炎症标志物及肺组织病理学的影响。方法健康SPF级SD雄性大鼠60只,分2、4、6 d 3种给药疗程,各疗程20只大鼠随机分为5组:空白对照组(control组)、模型组(model组)、塞来昔布组(Cox组)、莫西沙星组(Mox组)、塞来昔布+莫西沙星组(Cox+Mox组),每组4只。采用直视下气管插管接种肺炎克雷伯杆菌混悬液制作肺炎模型,control组予等量无菌生理盐水接种。药物治疗组在注射细菌混悬液后次日分别腹腔注射塞来昔布及莫西沙星,分别连续2、4、6 d。给药后第3、5、7天分批处死动物,使用ELISA法测定肺组织匀浆细胞因子、环氧化酶代谢产物及热休克蛋白90(HSP90)的水平;取肺组织进行病理学检查。结果2、4、6 d 3种给药疗程的各model组肺湿重/体重均较control组升高(P<0.05),3种给药疗程的各Cox+Mox组与control组比较差异无统计学意义(P>0.05),但均较model组降低(P<0.05)。给药4 d和6 d,model组的C反应蛋白(CRP)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-1β、转化生长因子(TGF)-β、HSP90、前列腺素I_(2)(PGI_(2))、前列腺素E_(2)(PGE_(2))、血栓素A_(2)(TXA_(2))均较control组升高(P<0.05),但IL-10较control组降低(P<0.05);塞来昔布、莫西沙星及两药联合均可降低CRP、TNF-α、IL-6、IL-1β、PGI_(2)、PGE_(2)、TXA_(2)(P<0.05),塞来昔布联合莫西沙星未显示出优于单独使用塞来昔布或莫西沙星。但塞来昔布联合莫西沙星可提高IL-10(P<0.05)。肺组织病理学显示各model组的肺组织均出现明显炎症细胞浸润、肺泡间质出血、局部机化物形成等改变,塞来昔布、莫西沙星及两药联合的上述病理改变均较模型组减轻。结论塞来昔布、莫西沙星及两药联合可降低肺炎克雷伯杆菌肺炎大鼠肺部致炎细胞因子和前列腺素代谢产物水平,塞来昔布联合莫西沙星可提高抗炎因子IL-10水平。与单用塞来昔布或莫西沙星相比,两药联合在降低致炎细胞因子水平及改善肺组织病变作用方面并无显著优势。

Objective To study the effect of combination of celecoxib and moxifloxacin on inflammatory markers and histopathology of lung in rats with Klebsiella pneumonia.Methods Sixty SD rats were randomly divided into 15 groups,according to the given drugs and course,in which the rats were given with placebo,celecoxib,moxifloxacin,celecoxib and moxifloxacin for 2,4 and 6 days.Pneumonia model was established by inoculating Klebsiella pneumonia suspension with endotracheal intubation under direct vision.On the 3rd,5th and 7th day after administration,the animals were sacrificed in batches.The levels of cytokines,cyclooxygenase metabolites and heat shock protein 90 were determined by ELISA.Lung tissues were taken for pathological examination.Results The lung wet weight/body weight of each model group was significantly heavier than that of the control group(P<0.05).After administering for 4 days and 6 days,the levels of CRP,TNF-α,IL-6,IL-1β,TGF-β,HSP90,PGI_(2),PGE_(2) and TXA_(2) in the model group were significantly higher than those in the control group(P<0.05),but the level of IL-10 was significantly lower than that in the control group(P<0.05).The levels of CRP,TNF-α,IL-6,IL-1β,PGI_(2),PGE_(2) and TXA_(2) in the drug treatment groups were significantly lower than those in the model group(P<0.05),but the level of IL-10 was significantly higher than that in the model group(P<0.05).Lung histopathology showed obvious alveolar interstitial inflammation,hemorrhage,and local organic matter formation in model groups.The above pathological changes were improved in the drug treatment groups.Conclusion Selective COX-2 inhibitor can reduce the levels of inflammatory factors in the lungs of rats with Klebsiella pneumonia,and improve the pathological changes of lung tissue.Compared with celecoxib or moxifloxacin alone,celecoxib combined with moxifloxacin has no significant advantage in reducing proinflammatory cytokine levels and improving lung lesions.