黏菌素对小鼠肾毒性及其机制的研究  

Nephrotoxicity induced by colistin and its mechanism in mice

作　　者：代重山[1] 李继昌[1] 李广兴[1] 李健 

机构地区：[1]东北农业大学动物医学学院,黑龙江哈尔滨150030 [2]Facility for Anti-infective Drug Development and Innovation,Monash Institute of Pharmaceutical Sciences,Monash University

出　　处：《中国兽医科学》2013年第3期320-324,共5页Chinese Veterinary Science

基　　金：国家自然科学基金资助项目(31272613);教育部留学回国人员科研启动基金项目(41);哈尔滨市科技创新人才研究专项资金留学回国人员项目(2012RFLXN005);黑龙江省教育厅科学技术项目(12521043)

摘　　要：为探究黏菌素对小鼠的肾毒性作用及其产生毒性的可能机制,将160只昆明系雌性小鼠分为4组,每组40只,即硫酸黏菌素高、中、低剂量组(静脉注射15.0、7.5、3.75mg/kg)和对照组(注射等量生理盐水),连续给药7d,并于第1、3、7和15天,测定小鼠血清肌酐(Cre)、尿素氮(BUN)及肾超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,并进行肾病理学半定量评价。结果发现,黏菌素可引起小鼠体重显著下降;与对照组相比,高剂量组给药3、7d后,血BUN、Cre显著升高,肾组织SOD活性显著降低(P<0.01),MDA含量显著增加(P<0.01),肾小管坏死,半定量评分分别为(2.4±0.89)分(P<0.01)、(3.6±1.14)分(P<0.01),均显著高于对照组。中剂量组于给药7d后生化指标及半定量评价均出现显著变化(P<0.05),低剂量组均未见显著变化。至给药后第15天,中剂量组肾损伤有所恢复,但高剂量组仍差异显著。证实黏菌素肾毒性具有明显的时间依赖性及剂量依赖性,氧化应激损伤可能是黏菌素肾毒性的重要机制之一。To investigate the toxic effect on kidney induced by colistin and its possible mechanism in mice, 160 female mice were randomly divided into the high-dose group（15 mg/kg）,middle-dose group（7.5 mg/kg） ,low-dose group（3.75 mg/kg） and the control group（9 g/L normal saline）. Colistin sulfate was ad- ministered intravenously for＇7 days. The blood BUN and Cre,the level of MDA and the activity of SOD in kidney and the semiquantitative score（SQS） of renal lesion were carried out on days 1,3,7 and 15. Com- pared with the control group, the body weights of mice treated by colistin reduced. On days 3 and 7, the level of blood BUN and Cre significantly increased,and the activity of SOD significantly decreased（P〈0.01） while the content of MDA significantly increased（P〈0.01） ,the acute tubular damage with necrosis of the tubular epithelial cells occurred and the SQS increased to （2.44-0.89）, （3.6_＋1.14） （both P%0.01） in the high-dose group. On day 7, in the middle-dose group, significant differences occurred in the levels of BUN, Cre and MDA and the activity of SOD,which had no significant difference in the low-dose group. On day 15, all the indexes presented a recovery tendency but the change of SOD and MDA were significantly different in the high-dose group and middle-dose group. The results revealed that the time-dependent and dose-dependent changes were induced in colistin induced-nephrotoxicity and the mechanism of oxidativestress may play an important role.

关 键 词：黏菌素 肾毒性 时间依赖性 剂量依赖性 氧化应激 

分 类 号：S859.82[农业科学—临床兽医学]