嗜酸乳杆菌缓解LPS诱导的急性肺炎小鼠肺部炎症及机制研究

Lactobacillus acidophilus alleviates lung inflammation in LPS-induced acute pneumonia in mice:efficacy and mechanism

目的探究嗜酸乳杆菌对脂多糖(LPS)诱导的急性肺炎小鼠的炎症的影响及可能的机制。方法将21只小鼠分为对照组(NC)、模型组(LPS)和嗜酸乳杆菌处理组(Probiotics)。NC组(n=6)小鼠正常喂养,LPS组(n=8)和Probiotics组(n=7)小鼠采用LPS(10 mg/kg)气管滴注法建立急性肺炎小鼠模型,Probiotics组小鼠给予嗜酸乳杆菌,7 d后处死小鼠。通过HE染色、肺组织湿/干质量比(W/D)评估肺组织的病理学改变;采用ELISA检测支气管肺泡灌洗液中的炎症因子水平和肺组织中髓过氧化物酶(myeloperoxidase,MPO)活性;16S rDNA测序检测肠道菌群的多样性;免疫组织化学染色评估ZO-1和TRPV4的表达。结果与LPS组相比,Probiotics组的W/D、炎症因子IL-1β、TNF-α、IL-6水平降低,IL-10升高(P<0.05);MPO活性减弱(P<0.05);结肠和肺组织中TRPV4表达下调,结肠组织ZO-1表达上调;同时螺杆菌属和脱硫弧菌属的丰度显著改变。结论嗜酸乳杆菌能显著减轻LPS诱导的小鼠肺部炎症,可能与肠道内脱硫弧菌属丰度、TRPV4通道活性和肠黏膜屏障通透性有关。

Objective To investigate the effect of Lactobacillus acidophilus(L.acidophilus)on the inflammation of mice with lipopolysaccharide(LPS)-induced acute pneumonia and the possible mechanism.Methods Twenty-one mice were divided into a control group(NC,n=6),a model group(LPS,n=8)and a L.acidophilus-treated group(Probiotics,n=7).The mice in the control group were fed normally,while those in the LPS and Probiotics groups were treated with 10 mg/kg LPS through tracheal drip to establish a mouse model of acute pneumonia,and those in the Probiotics group were given L.acidophilus.All of the mice were executed in 7 d after modeling.The pathological changes of lung tissue were assessed by HE staining and wet/dry ratio(W/D)of lung tissue.ELISA was used to detect the levels of inflammatory factors in bronchoalveolar lavage fluid and the activity of myeloperoxidase(MPO)in lung tissue.16S rDNA sequencing was employed to observe the diversity of intestinal flora,and immunohistochemical(IHC)staining was applied to determine the expression of ZO-1 and TRPV4.Results The Probiotics group had significantly reduced W/D ratio and IL-1β,TNF-αand IL-6 levels,increased IL-10 level(P<0.05),diminished MPO activity(P<0.05),down-regulated TRPV4 expression in colon and lung tissues,and upregulated ZO-1 expression in colon tissue,meanwhile,the abundance of Helicobacter spp.and Desulfovibrio spp.was significantly altered when compared with the LPS group.Conclusion L.acidophilus alleviates lung inflammation in LPS-induced pneumonia in mice,which may be associated with intestinal abundance of Desulfovibrio spp.in the,activity of TRPV4 channel and intestinal mucosal permeability.