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载头孢喹肟微球制剂对肺炎克雷伯菌感染大鼠肺炎及炎症反应的保护作用

Cefquinome-Loaded Microsphere Formulations in Protection against Pneumonia with Klebsiella pneumonia Infection and Inflammatory Response in Rats.

机构信息

College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, 266109, China.

National-Local Joint Engineering Laboratory of Agricultural Bio-pharmaceutical Technology, Qingdao, 266109, China.

出版信息

Pharm Res. 2019 Mar 28;36(5):74. doi: 10.1007/s11095-019-2614-7.

DOI:10.1007/s11095-019-2614-7
PMID:30923922
Abstract

PURPOSE

This study aimed to compare in vivo activity between cefquinome (CEQ)-loaded poly lactic-co-glycolic acid (PLGA) microspheres (CEQ-PLGA-MS) and CEQ injection (CEQ-INJ) against Klebsiella pneumonia in a rat lung infection model.

METHODS

Forty-eight rats were divided into control group (sham operated without infection and drug treatment), Klebsiella pneumonia model group (KPD + Saline), CEQ-PLGA-MS and CEQ-INJ therapy groups (KPD + CEQ-PLGA-MS and KPD + INJ, respectively). In the KPD + Saline group, rats were infected with Klebsiella pneumonia ATCC 10031. In the KPD + CEQ-PLGA-MS and KPD + INJ groups, infected rats were intravenously injected with 12.5 mg/kg body weight CEQ-PLGA-MS and CEQ-INJ, respectively.

RESULTS

Compared to CEQ-INJ treatment group, CEQ-PLGA-MS treatment further decreased the number of bacteria colonies (decreased to 1.94 lg CFU/g) in lung tissues and the levels of inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-4 (p < 0.05 or p < 0.01) in bronchoalveolar lavage fluid at 48 h. Consistently, a significant decreases of scores of inflammation severity were showed at 48 h in the KPD + CEQ-PLGA-MS treatment group, compared to the KPD + CEQ-INJ treatment group.

CONCLUSION

Our results reveal that CEQ-PLGA-MS has the better therapeutic effect than CEQ-INJ for Klebsiella pneumonia lung infections in rats. The vehicle of CEQ-PLGA-MS as the promising alternatives to control the lung infections with the important pathogens.

摘要

目的

本研究旨在比较头孢喹肟(CEQ)负载聚乳酸-羟基乙酸共聚物(PLGA)微球(CEQ-PLGA-MS)与 CEQ 注射液(CEQ-INJ)在肺炎克雷伯菌大鼠肺部感染模型中的体内活性。

方法

将 48 只大鼠分为对照组(假手术,无感染和药物治疗)、肺炎克雷伯菌模型组(KPD+生理盐水)、CEQ-PLGA-MS 和 CEQ-INJ 治疗组(KPD+CEQ-PLGA-MS 和 KPD+INJ,分别)。在 KPD+生理盐水组,大鼠感染肺炎克雷伯菌 ATCC 10031。在 KPD+CEQ-PLGA-MS 和 KPD+INJ 组,感染大鼠分别静脉注射 12.5mg/kg 体重的 CEQ-PLGA-MS 和 CEQ-INJ。

结果

与 CEQ-INJ 治疗组相比,CEQ-PLGA-MS 治疗组进一步降低了肺组织中细菌菌落数量(降至 1.94 lg CFU/g)和支气管肺泡灌洗液中炎症细胞因子 TNF-α、IL-1β、IL-6、IL-4 的水平(p<0.05 或 p<0.01),在 48 小时。同样,在 KPD+CEQ-PLGA-MS 治疗组,与 KPD+CEQ-INJ 治疗组相比,在 48 小时时炎症严重程度评分显著降低。

结论

我们的结果表明,CEQ-PLGA-MS 对肺炎克雷伯菌肺部感染的治疗效果优于 CEQ-INJ。CEQ-PLGA-MS 的载体为控制重要病原体引起的肺部感染提供了有前途的替代方案。

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