磷霉素对万古霉素致大鼠肾损害的保护作用及机制研究  

The effect and mechanism of fosfomycin on vancomycin-induced kidney injury in rats

作　　者：黄丽蓓 杨斌[2] 黄晓青[1] 林子杰 李洁静 唐生平 丘岳[1,2] Huang Libei;Yang Bin;Huang Xiaoqing;Lin Zijie;Li Jiejing;Tang Shengping;Qiu Yue(The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Department of Pharmacy,Guangxi Medical University,Nanning 530021,China;The First Clinical Medical College,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院,南宁530021 [2]广西医科大学药学院,南宁530021 [3]广西医科大学第一临床医学院,南宁530021

出　　处：《广西医科大学学报》2021年第11期2054-2057,共4页Journal of Guangxi Medical University

基　　金：广西教育厅高校中青年教师科研基础能力提升项目(No.2019KY0131);广西壮族自治区卫生健康委课题(No.Z20190075)。

摘　　要：目的:研究磷霉素对万古霉素致大鼠肾损害(KI)的影响及其机制。方法:将60只SD大鼠随机分为6组,即空白对照组、磷霉素对照组、KI组和KI+磷霉素低、中、高剂量组,每组10只。腹腔注射200 mg/kg万古霉素建立KI模型。磷霉素对照组仅腹腔注射250 mg/kg磷霉素,空白对照组腹腔注射等量生理盐水。测定血清中胱抑素C(Cys C)、肌酐(Scr)、尿素氮(BUN)和肾组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)水平,并观察肾组织的病理变化。结果:与空白对照组比较,KI组大鼠血清中Cys C、Scr、BUN水平及肾组织中MDA、NO水平明显升高,肾组织SOD活性明显降低(P<0.01),大鼠肾小管出现不同程度的变性和坏死,呈肾小管—间质性肾炎。与KI组比较,磷霉素各剂量组大鼠血清中Cys C、Scr、BUN水平及肾组织中MDA、NO水平均不同程度降低,且肾组织中SOD水平明显升高,肾脏的病理变化明显减轻。空白对照组与磷霉素对照组各指标比较,差异无统计学意义(P>0.05)。结论:磷霉素能有效改善万古霉素所致大鼠KI,其机制可能与抑制大鼠体内的氧化应激反应有关。Objective:To explore the effect and mechanism of fosfomycin on vancomycin-induced kidney injury(KI) in rats.Methods:Sixty rats were randomly divided into 6 groups:blank control group,fosfomycin control group,KI group,KI+low-dose fosfomycin group,KI+medium-dose fosfomycin group,and KI+high-dose fosfomycin group,with 10 rats in each group.KI model was established by intraperitoneal injection of 200 mg/kg vancomycin.The rats in fosfomycin control group were intraperitoneally injected with 250 mg/kg fosfomycin,and rats in blank control group were intraperitoneally injected with the equal volume of normal saline.The levels of cystatin C(Cys C),creatinine(Scr),and urea nitrogen(BUN) in serum and the contents of superoxide dismutase(SOD),malondialdehyde(MDA),and nitric oxide(NO) in renal tissues were determined.The pathological changes of renal tissues were observed.Results:Compared with the blank control group,the levels of Cys C,Scr and BUN in serum and the contents of MDA and NO in renal tissues in the KI group were significantly increased,while the SOD activity was significantly decreased(P<0.01).The renal tubules of model group rats exhibited different degrees of degeneration and necrosis,showing tubular-interstitial nephritis.Compared with the KI group,the pathological changes of kidney were alleviated,the levels of Cys C,Scrc,BUN,MDA and NO were significantly decreased,and the SOD activity was markedly increased(P<0.05).Conclusion:Fosfomycin can effectively inhibit renal damage induced by vancomycin in rats,and the mechanism may be related to the inhibition of oxidative stress in rats.

关 键 词：磷霉素 万古霉素 肾损害 氧化还原 

分 类 号：R965[医药卫生—药理学]