阿奇霉素對哮喘小鼠氣道炎癥及細胞因子表達的影響

楊軍霞　郭英萌

[摘要] 目的 觀察支氣管哮喘小鼠炎性細胞因子表達，探討阿奇霉素對肺部炎癥及細胞因子表達的影響。 方法 6～8周齡的雌性BALB/c小鼠32只，采用隨機數字表法將其分為四組，A組：生理鹽水對照組;B組：哮喘組;C組：阿奇霉素干預組;D組：地塞米松干預組，每組8只。分別于第0、7、14天予B、C、D組小鼠腹腔注射雞卵白蛋白（OVA）25 μg+Al（OH）3 1 mg。致敏1周后，2%OVA生理鹽水溶液霧化吸入激發。A組予等量生理鹽水代替OVA致敏和激發，激發6 d。C組于第14天起，霧化吸入1 h后皮下注射阿奇霉素0.4 mg/mL，連續7 d。D組于第14天起，霧化吸入1 h后皮下注射地塞米松磷酸鈉2 mg/kg，連續7 d。激發后24 h，觀察各組小鼠肺組織病理表現，收集左肺支氣管肺泡灌洗液（BALF）。采用酶聯免疫吸附法（ELISA）檢測白細胞介素-8（IL-8）、腫瘤壞死因子-α（TNF-α）、嗜酸性粒細胞（EOS）百分比及白細胞計數。 結果 B、C、D組小鼠成功造模，存在哮喘發作癥狀及氣道炎癥病理表現。與A組比較，B組小鼠BALF中白細胞總數、EOS百分比、IL-8及TNF-α含量均顯著升高，差異有高度統計學意義（P < 0.01）。與B組比較，C組和D組小鼠BALF中白細胞總數、EOS百分比、IL-8及TNF-α含量均顯著降低，差異有高度統計學意義（P < 0.01）。C、D兩組各項指標比較，差異均無統計學意義（P > 0.05）。 結論 阿奇霉素可以抑制IL-8、TNF-α的表達，阻礙Th2型細胞因子的生成，緩解氣道炎癥。

[關鍵詞] 支氣管哮喘;阿奇霉素;炎癥;細胞因子

[中圖分類號] R562 ? ? ? ? ?[文獻標識碼] A ? ? ? ? ?[文章編號] 1673-7210（2019）06（c）-0021-04

Effects of Azithromycin on airway inflammation and cytokine expression in bronchial asthma mice

YANG Junxia ? GUO Yingmeng

Department of Pediatrics， Linyi Central Hospital， Shandong Province， Linyi ? 276400， China

[Abstract] Objective To observe the expression of inflammatory cytokines in bronchial asthma mice， and to explore the effect of Azithromycin on the expression of pulmonary inflammation and inflammatory cytokines. Methods According to random number table， 32 female BALB/c mice aged 6-8 weeks were randomly divided into four groups： group A， normal saline control group; group B， asthma group; group C， Azithromycin intervention group; group D， Dexamethasone intervention group， with 8 mice in each group. Mice in group B， C and D were intraperitoneally injected with ovalbumin （OVA） 25 μg （OH）3 1 mg at 0， 7， 14 days， respectively. After sensitization for 1 week， 2% OVA solution was nebulized and inhaled. Group A was sensitized and stimulated with normal saline instead of OVA for 6 days. In group C， Azithromycin （0.4 mg/mL） was injected subcutaneously 1 hour after atomization inhalation at day 14 consecutively for 7 days. In group D， 2 mg/kg of Dexamethasone Sodium phosphate was injected subcutaneously 1 hour after atomization inhalation at day 14 consecutively for 7 days. The pathological manifestations of lung tissues in each group were observed 24 hours after stimulation， and the left bronchoalveolar lavage fluid （BALF） was collected， and the percentage of interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， eosinophilic granulocytes （EOS） and white blood cell count were detected by enzyme linked immunosorbent assay （ELISA）. Results Mice in group B， C and D were successfully modeled and presented asthma attack symptoms and pathological manifestations of airway inflammation. Compared with group A， the total number of white blood cells， percentage of EOS， IL-8 and TNF-α contents in BALF of mice in group B were significantly increased， with statistically significant differences （P < 0.01）. Compared with group B， the total number of white blood cells， percentage of EOS， IL-8 and TNF-α contents in BALF of group C and group D were significantly reduced， with statistically significant differences （P < 0.01）. There were no statistically significant differences in the indicators between group C and D （P > 0.05）. Conclusion Azithromycin can inhibit the expression of IL-8 and TNF-α， inhibit the production of Th2 cytokines， and relieve airway inflammation.

[Key words] Bronchial asthma; Azithromycin; Inflammation; Cytokines

支氣管哮喘是一種氣道慢性炎癥性疾病，Th2細胞在誘導和維持免疫炎癥過程中起重要的作用。Th2細胞主要分泌白細胞介素-8（IL-8）、腫瘤壞死因子-α（TNF-α）等促進IgE的合成、嗜酸性粒細胞（EOS）的生長與分化，以及黏液分泌、氣道高反應（AHR）的發生。氣道平滑肌細胞（ASMCs）具有收縮功能及分泌功能，能分泌趨化因子、細胞因子等多種炎性介質，對氣道炎癥的發生及發展起著重要的作用。……