黄芩苷联合美罗培南对小鼠腹腔铜绿假单胞菌早期生物被膜的体内影响

In vivo effect of baicalin combined with meropenem on early biofilm of Pseudomonas aeruginosain abdominal cavities of mice

目的构建小鼠腹腔铜绿假单胞菌(PAE)早期生物被膜(BF)感染模型,探讨黄芩苷(Baicalin)联合美罗培南(MEM)对PAE体内早期BF感染的作用。方法以输液管为载体,PAO1野生株为实验菌株,32只雌性小鼠随机分为空白对照组、Baicalin组(60mg/Kg·d)、MEM组(50mg/Kg·d)、Baicalin(60mg/Kg·d)+MEM(50mg/Kg·d)组,建立小鼠腹腔BF感染模型后开始腹腔注射上述药物,空白对照组用等量无菌生理盐水;药物作用24h后行连续稀释法载体表面活菌计数,扫描电子显微镜(SEM)观察载体表面BF形态变化。结果药物干预24h,药物单独作用组或联合组载体表面菌落计数均少于空白对照组(P<0.01);MEM组较Baicalin组减少(P<0.01);Baicalin+MEM组均较Baicalin组、MEM组明显减少(P<0.01);空白对照组SEM观察载体表面细菌均比Baicalin组、MEM组、Baicalin+MEM组形成的BF多而稠厚;MEM组较Baicalin组稀薄;Baicalin+MEM组BF基本被破坏清除,仅见少量PAE细菌粘附。结论 Baicalin对小鼠腹腔PAE早期BF具有破坏作用,与MEM联合应用可显著增强其对BF的杀菌作用。

OBJECTIVE To establish an experimental murine model of intra-abdominal infection with Pseudomonas aeruginosa early biofilm （BF） and explore the effect of baicalin combined with meropenem on intra-abdominal early BF infection with P. aeruginosa. METHODS With the infusion tube set as the carrier, the PA01 wild strains taken as the experimental strains, 32 female mice were randomly divided into the blank control group, the MEM group （50 mg/Kg · d）, and the Baicalin（60 mg/Kg · d） plus MEM（50 mg/Kg · d） group, the intraperitoneal injection of the above drugs was conducted after the model of mice with intra-abdominal BI infection was established, the blank control group was treated with same amount of sterile saline. The viable bacterial counts on the carriers＇ sur- faces were determined by serial dilution after the drug action for 24 hours, and the morphological changes of the BF on the surfaces of the carriers were observed by means of scanning electron microscopy （SEM）. RESULTS The bacterial colony counts on the carriersr surfaces were less in the single drug action group or the combined drugs ac- tion group than in the blank control group after the drug intervention for 24 hours （P〈0.01）. The bacterial colony counts were less in the MEM group than in the Baicalin group （P〈0.01） ; the bacterial colony counts were re- markably less in the Baicalin plus MEM group than in the Baicalin group and the MEM group （P〈0.01）. The SEM observation revealed that the bacterial BF formed on the surfaces of carries was more and thicker in the blank control group than in the Baicalin group, the MEM group, and the Baicalin plus MEM group and was thinner in the MEM group than in the Baicalin group; the biofilms of the Baicalin plus MEM group were almost destroyed and cleared, only a small amount of P. aeruginosa strains could be seen. CONCLUSION Baicalin has the destructive effect on early BF of the intra-abdominal P. aeruginosa in the mice, and its combination with MEM may intensify the bactericidal action against BF.