磷霉素对异帕米星致铜绿假单胞菌生物被膜局部感染大鼠肾毒性的影响

The Effect of Fosfomycin on the Renal Toxicity Induced by Isepamicin in Rat Tissue Cage Infection Model Caused by Ps. Aeruginosa Biofilm

目的通过磷霉素与异帕米星联合应用于铜绿假单胞菌生物被膜感染的大鼠模型,观察磷霉素对异帕米星致大鼠肾毒性的影响。方法采用组织笼皮下埋植法建立大鼠铜绿假单胞菌生物被膜体内局部感染动物模型;大鼠随机分为4组:健康对照组、氯化钠注射液组、阳性对照组(异帕米星300mg·kg-1)和联合用药组,每组6只;采用腹腔给药,分别检测给药前,给药2周和4周时,大鼠的血清肌酐(SCr)、血尿素氮(BUN)、尿量(UPD)、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG);4周时处死大鼠做肾组织病理标本光镜及透射电镜(TEM)观察。结果随给药时间的延长,异帕米星组和联合用药组的SCr、BUN及NAG酶水平均增高。4周时联合用药组的SCr、BUN及NAG酶水平与对照组相比升高,但差异无统计学意义(P>0.05),而异帕米星组与对照组、联合用药组相比显著升高(P<0.05)。4周时的肾组织光镜观察和肾组织透射电镜观察显示:联合用药组的肾损害较异帕米星单药组显著减轻。结论研究发现磷霉素可减轻异帕米星致肾毒性作用。

Objective To evaluate the effect of cage infection model caused by Ps. Aeruginosa fosfomycin on the renal toxicity induced by isepamicin in rat tissue biofilm. Methords The tissue cage method was used to establish the animal model of local Ps. Aeruginosa biofilm infection. Rats were randomly divided into 4 groups： control group, negative control group, positive control group（isepamicin 300 mg·kg^-1） and fosfomycin and isepamicin group, 6 rats each group. Renal toxicity indexes such as serum creatinine（SCr）, blood urea nitrogen（BUN）, urinary production（UPD） and urine n-acetyl-β-d-glucosaminidase（NAG） were determined at 0, 2 and 4 weeks after abdominal cavity administration. At last observed nephridial tissue pathology through light microscope and transmission electron microscope （TEM）. Results Tissue cage experiment in rat showed that the level of SCr, BUN and NAG of the combination group were raised up than control groups after administration for 4 weeks but no significant differences statistically （P〉0.05）, and those of the isepamicin group were raised up remarkably than other groups（P〈0.05）. At 4 weeks the nephridial tissue pathology results which were observated through light microscope and TEM showed the level of renal damage induced by the group offosfomycin and isepamicin were lower than that of the group（P〈0.05）. Conclusion The animal experiment showed that fosfomycin may relieve renal damage induced by isepamicin.