氨溴索在保护氟康唑所致大鼠肺组织损伤中的作用及机制研究

目的 研究氨溴索对气管内注射氟康唑所致大鼠肺组织损伤的保护作用及肿瘤坏死因子α(TNF-α)在肺组织中的表达变化及意义.方法 将90只雄性SD大鼠随机平均分成3组,分别为正常对照组(N组)、氟康唑组(F组)、氟康唑+盐酸氨溴索干预组(FA组).除N组外均行气管穿刺注入氟康唑,FA组气管内给药前6h腹腔注射氨溴索,于6个时间点(2h、1d、2d、3d、5d、7 d)分别处死大鼠5只,取右肺副叶行HE染色观察肺组织病理变化和免疫组化检测肺组织TNF-α蛋白的表达变化.结果 病理结果提示F组和FA组肺泡内均有中性粒细胞浸润,F组气管、血管周围及肺泡内炎症细胞浸润最明显.免疫组化提示F组2h时染色最浅,TNF-α蛋白的表达从2h开始至第3天逐渐增强,第3天时着色最深;F组各时间点TNF-α蛋白染色程度评分均高于FA组和N组,差异有统计学意义(P值均＜0.01).结论 气管内局部使用氟康唑可对大鼠肺组织造成损伤,并使肺组织TNF-α蛋白的表达升高,氨溴索对该损伤具有保护作用,可能与下调TNF-α蛋白的表达相关.

Function and mechanism researches of ambroxol in protecting lung injury caused by fluconazole in rats

Objective To observe the protection effects of ambroxol on lung injury of rats caused by intratracheal instillation of fluconazole and the expression of tumor necrosis factor-α(TNF-α) in lung tissue.Methods 90 male SD rats were randomly divided into three groups (30 rats in each group),including normal control group (N group),fluconazole group (F group) and fluconazole and ambroxol hydrochloride intervention group (FA group).No treatment was given in N group,the rats in F group and FA group were injected the fluconazole through tracheal puncture.The rats in FA group were intraperitoneally injected with ambroxol hydrochloride six hours before intratracheal instillation of fluconazole.Five rats in each group were killed at six time points (2 h,1 d,2 d,3 d,5 d,7 d).And then the right deputy lung lobes of rats were dissected to observe the pathological changes by HE staining and to examine the expression of TNF-α in lung tissue by immunohistochemical method.Results HE staining result of lung tissue showed that the alveolar spaces of both F group and FA group were infiltrated by neutrophil granulocyte,and the infiltration of inflammatory cells was more serious around tracheal mucosa,blood vessels and in the alveolar spaces in F group.The result of immunohistochemistry demonstrated that the staining was the most shallow at the second hour in F group.Nevertheless,the expression of TNF-α increased gradually from the second hour to the third day and reached a peak on the third day.The staining score of TNF-α at the six time points of FA group was higher than that of F group and N group (all P ＜0.01).Conclusions Intratracheal instillation of fluconazole can induce lung injury of rats and can increase the expression of TNF α in lung tissue.Ambroxol can alleviate the damage,which may be related with down-regulation of the expression of TNF-α.