新鱼腥草素钠对小鼠鲍曼不动杆菌肺感染模型的保护作用

Protective Effect of Sodium New Houttuyfonate Against Acinetobacter baumannii Pulmonary Infection in Mice

目的构建小鼠鲍曼不动杆菌诱导的肺炎模型,观察新鱼腥草素钠对鲍曼不动杆菌肺部感染的保护作用。方法将小鼠分为对照组、肺炎模型组、低剂量新鱼腥草素钠组和高剂量新鱼腥草素钠组。术前4d和1d利用环磷酰胺预处理各组C57BL/6小鼠,从术前3d开始,低剂量新鱼腥草素钠组和高剂量新鱼腥草素钠组每天给予新鱼腥草素钠治疗,使用重症监护病房分离的鲍曼不动杆菌菌株制备新鲜菌液,通过气道接种方法接种至小鼠制备鲍曼不动杆菌肺感染模型,分别于接种后24、72h进行小鼠肺及血液细菌计数,苏木精-伊红染色观察肺组织炎症变化,检测支气管肺泡冲洗液(bronchoalveolar lavage fluid,BALF)白细胞、中性粒细胞数量以及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)的水平。结果小鼠接种鲍曼不动杆菌后肺及血液中细菌数量增多(P<0.05);小鼠肺部有严重的炎性反应和组织损伤,BALF中白细胞计数升高(P<0.05),TNF-α、IL-1β含量增加。而经过新鱼腥草素钠治疗后,小鼠肺及血液中细菌数量显著低于肺炎模型组,肺组织损伤较轻,BALF中白细胞、中性粒细胞以及TNF-α、IL-1β水平均显著升高(P<0.05)。结论新鱼腥草素钠能够显著提高鲍曼不动杆菌感染小鼠的白细胞数量和活性,从而增强抗感染能力。

Objective To establish a mouse model of pneumonia induced by Acinetobacter baumannii,and to investigate the protective effect of sodium new houttuyfonate against Acinetobacter baumannii pulmonary infection.Methods Mice were divided into control group,pneumonia model group,and low-and highdose sodium new houttuyfonate groups.C57 BL/6 mice were pretreated with cyclophosphamide on days 4 and 1 before surgery,and since day 3 before treatment,the mice in the low-and high-dose sodium new houttuyfonate groups were given sodium new houttuyfonate.The Acinetobacter baumannii strain isolated in the clinical ICU was used to prepare fresh bacterial solution,and airway inoculation was performed to establish a mouse model of Acinetobacter baumannii pulmonary infection.Bacterial count in the lung and blood was determined at 24 and 72 hours after inoculation.Hematoxylin and eosin staining was used to observe inflammatory changes in lung tissue.The numbers of leukocytes and neutrophils and the levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β )in bronchoalveolar lavage fluid(BALF)were measured.Results There was a significant increase in the number of bacteria in the lung and blood after the inoculation with Acinetobacter baumannii in mice(P<0.05),and the mice had serious inflammatory response and tissue injury,as well as significant increases in leukocyte count and levels of TNF-αand IL-1β in BALF(P<0.05).After the treatment with sodium new houttuyfonate,compared with the pneumonia model group,the low-and high-dose sodium new houttuyfonate groups had significantly lower numbers of bacteria in the lung and blood,significantly milder lung tissue injury,and significant increases in the numbers of leukocytes and neutrophils and the levels of TNF-αand IL-1β in BALF(P<0.05).Conclusion Sodium new houttuyfonate can significantly increase the number and activity of leukocytes in mice with Acinetobacter baumannii pulmonary infection and thus enhance anti-infection ability.