新型牛蛙抗菌肽Temporin-La对金黄色葡萄球菌感染模型小鼠的治疗效果  

Curative effect of novel Rana catesbeiana antimicrobial peptide Temporin-La on Staphylococcus aureus infection in mouse model

作　　者：赵瑞利[1,2] 韩文瑜[1] 韩俊友[1] 金天明[2] 冯新[1] 雷连成[1] 孙长江[1] 王选[2] 

机构地区：[1]吉林大学畜牧兽医学院,吉林长春130062 [2]天津农学院动物科学系,天津300384

出　　处：《中国生物制品学杂志》2013年第8期1143-1146,1150,共5页Chinese Journal of Biologicals

基　　金：国家自然科学基金资助项目(31201886);天津农学院科技发展基金计划(2011D03;2012N18)

摘　　要：目的探讨新型牛蛙抗菌肽Temporin-La对金黄色葡萄球菌感染模型小鼠的治疗效果。方法采用二倍稀释法检测抗菌肽Temporine-La对临床主要致病菌的最小抑菌浓度(minimum inhibitory concentration,MIC);透射电镜观察Temporine-La对金黄色葡萄球菌的作用效果;复制金黄色葡萄球菌表皮感染小鼠模型,分别用4 U/ml青霉素和10μg/ml Temporin-La进行治疗,另设生理盐水对照组和空白对照组,感染后第4天,对各组小鼠进行白细胞计数、细菌计数、血管内皮生长因子(vascular endothelial growth factor,VEGF)表达水平检测及病理组织切片观察。结果Temporin-La对革兰阳性菌的抑菌活性高于革兰阴性菌,其中对金黄色葡萄球菌的抑制作用最强;透射电镜观察显示,经100μg/ml Temporin-La处理的金黄色葡萄球菌出现了质壁分离的现象,细胞壁缺失或发生裂解,金黄色葡萄球菌发生裂解而死亡;感染后第4天,青霉素组和Temporin-La组白细胞数及创面下肌肉组织细菌数均明显低于生理盐水对照组(P<0.05或P<0.01),Temporin-La组小鼠血清VEGF的表达水平明显高于青霉素组和空白对照组(P<0.05),青霉素组和Temporin-La组小鼠的创口修复情况明显优于生理盐水对照组。结论 Temporin-La具有抗小鼠金黄色葡萄球菌感染的效果,为其临床应用提供了实验依据,也为抗感染治疗提供了新的思路。Objective To investigate the curative effect of a novel Rana catesbeiana antimicrobial peptide Temporin-La on Staphylococcus aureus infection in mouse model.Methods The minimum inhibitory concentration（MIC）of Temporine-La to major pathogens in clinic was determined by 2-fold dilution.The inhibitory effect of Temporine-La on S.aureus was observed by transmission electron microscopy.Mouse model of epidermal S.aureus infection was copied,and treated with 4 U / ml penicillin and 10 μg / ml Temporin-La respectively,using physiological saline as control.The mice untreated was served as blank control.The mice in various groups were observed for leukocyte count,bacterial count,expression level of vascular endothelial growth factor（VEGF）and histopathology on day 4 after infection.Results The inhibitory activity of Temporin-La to Gram positive bacteria was higher than that to Gram negative ones,of which that to S.aureus was the highest.Transmission electron microscopy showed plasmolysis in S.aureus treated with 100 μg / ml,expressed as disappearance or lysis of cell wall and death of S.aureus due to lysis.The leukocyte and bacterial counts of mice on day 4 after infection in penicillin and Temporin-La groups were significantly lower than those in physiological saline control group（P 0.05 or P 0.01）.However,the expression level of VEGF in sera of mice in Temporin-La group was significantly higher than those in penicillin and blank control groups（P 0.05）.The wound healing of mice in penicillin and Temporin-La group were superior to that in physiological saline control group.Conclusion Temporin-La showed curative effect on S.aureus infection in mice,which provided an experimental basis for clinical application of Temporin-La and a novel route for treatment of S.aureus infection.

关 键 词：牛蛙 抗菌肽 Temporin-La 金黄色葡萄球菌 感染 模型 动物 

分 类 号：R978.16[医药卫生—药品]