左氧氟沙星对肺结核大鼠肺泡巨噬细胞吞噬能力的影响及机制

Effect of levofloxacin on the phagocytic ability of alveolar macrophages in pulmonary tuberculosis rats and its mechanism

目的探讨左氧氟沙星对肺结核大鼠肺泡巨噬细胞吞噬能力的影响及机制。方法60只成熟清洁级雌性SD大鼠,体重180~200 g,通过胸腔注射结核分枝杆菌(H37Rv)悬液制备肺结核模型。将成功建模的肺结核大鼠(n=54)按照随机数字表法平分为3组-模型组、异烟肼组与左氧氟沙星组,分别给予异烟肼、异烟肼联合左氧氟沙星、生理盐水治疗,持续30 d。观察与测定3组大鼠在治疗第1天、第15天与第30天的体重。治疗第30天,检测肺泡巨噬细胞的平均荧光强度和吞噬阳性细胞百分比。治疗第30天,测定叉形头转录因子O亚型3(FoxO3)、巨噬细胞移动抑制因子(MIF)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)基因与蛋白相对表达水平。结果3组治疗第15天与第30天的体重均高于治疗第1天(P<0.05),异烟肼组与左氧氟沙星组高于模型组,左氧氟沙星组高于异烟肼组,差异均有统计学意义(P<0.05)。异烟肼组与左氧氟沙星组治疗第30天的巨噬细胞平均荧光强度、吞噬阳性细胞百分比均高于模型组,左氧氟沙星组高于异烟肼组,差异均有统计学意义(P<0.05)。异烟肼组与左氧氟沙星组治疗第30天的肺组织FoxO3、MIF、PI3K、Akt基因与蛋白相对表达水平均高于模型组,左氧氟沙星组高于异烟肼组,差异均有统计学意义(P<0.05)。结论左氧氟沙星在肺结核大鼠的应用能激活PI3K/Akt、FoxO3/MIF信号通路,提高肺泡巨噬细胞吞噬能力,促使大鼠体重的恢复。

Objective To investigate the effect and mechanism of levofloxacin on the phagocytic ability of alveolar macrophages in pulmonary tuberculosis rats.Methods Sixty mature and clean female SD rats,weighing 180~200 g,were injected into the chest cavity of Mycobacterium tuberculosis(H37Rv)suspension to prepare pulmonary tuberculosis models.Pulmonary tuberculosis rats(n=54)were divided into 3 groups according to the random number table method-model group,isoniazid group and levofloxacin group.They were treated with isoniazid,isoniazid combined with levofloxacin and normal saline for 30 days.The body weights of the three groups of rats on the first day,the 15th day and the 30th day were observed and measured.On the 30th day of treatment,the average fluorescence intensity of alveolar macrophages and the percentage of phagocytic-positive cells were detected.On the 30th day of treatment,the relative expression of genes and proteins of fork head transcription factor O subtype 3(FoxO3),macrophage migration inhibitory factor(MIF),phosphatidylinositol 3-kinase(PI3K),and protein kinase B(Akt)level were determined.Results The body weights of the three groups were higher on the 15th and 30th day of treatment(P<0.05),the isoniazid group and levofloxacin group were higher than the model group,and the levofloxacin group were higher than the isoniazid group,the differences were statistically significant(P<0.05).The average fluorescence intensity of macrophages and the percentage of phagocytic positive cells in the isoniazid group and levofloxacin group were higher than the model group on the 30th day of treatment,and the levofloxacin group were higher than the isoniazid group,the differences were statistically significant(P<0.05).The relative expression level of FoxO3,MIF,PI3K and Akt genes and proteins in the lung tissue in the isoniazid group and levofloxacin group were higher than those in the model group on the 30th day,and the levofloxacin group were higher than that in the isoniazid group,the differences were statistically significant(P<0.05).Conclusion The application of levofloxacin in pulmonary tuberculosis rats can activate the PI3K/Akt and FoxO3/MIF signaling pathways,improve the phagocytic ability of alveolar macrophages,and promote the recovery of rat body weight.