硫酸黏菌素对小鼠坐骨-胫神经毒性作用的电生理表现

Electrophysiological changes for toxic effect of colistin sulphate on sciatic-tibial nerves in mice

目的探讨硫酸黏菌素对小鼠坐骨-胫神经的毒性作用。方法昆明系雌性小鼠尾静脉注射硫酸黏菌素7.5 mg·kg-1,每12 h 1次,按取材时间分为给药1,3,7 d组及给药7 d停药7 d组。分别于第2和第4天给药前、第8和第15天(以第1次给药当天为第1天计)观测小鼠的体质量、步态、后肢支撑力、坐骨-胫神经的复合动作电位阈强度(TI)、最大刺激强度(MI)、潜伏期(CAPL)、波幅(CAPA)、时程(CAPD)、传导速率(NCV)以及血清肌酐(Cre)、尿素氮(BUN)的变化情况。结果与正常对照组相比,硫酸黏菌素给药1 d组,血清Cre显著升高,给药3 d组,体质量及BUN出现显著性差异,给药7 d组,步态、后肢支撑力出现显著性差异。给药1,3和7 d组,坐骨-胫神经动作电位各参数随时间发生改变,TI显著增加,分别为60%,60%,193%(P<0.01);MI显著增加,分别为4%,13%和100%(P<0.05);CAPL显著增加,分别为9.0%,9.0%和14.6%(P<0.05),CAPA降低,分别为0.92%,16.2%和47.6%(P<0.01);CAPD显著增加,分别为15.1%,11.5%和52.8%(P<0.05);NCV显著减低,分别为7.6%,7.5%和12.7%(P<0.05);停药7 d组,步态及后肢支撑力较正常对照组无明显差异,电生理各参数均有所恢复,且只有CAPA较正常对照组差异显著(P<0.05)。结论硫酸黏菌素肾毒性较神经毒性先发生,小鼠坐骨-胫神经动作电位随给药时间延长发生进行性变化,且CAPA持续时间最长。

OBJECTIVE To investigate the toxic actions of colistin sulphate on sciatic-tibia1 nerves of mice. METHODS Colistin sulphate 7.5 mg · kg-1 was iv administered to Kunmingfemale mice, twice a day. The mice were divided into colistin sulphate 1, 3, 7 d and 7 d post colistin sulphate groups according the adminstration for 1, 3 and 7 d, respectively. The body mass and gait observations were obtained first, followed by determinations of foot splay and the threshold intensity （TI）, maximal intensity （MI）, compound action potential duration （CAPD）, latency of compound action potential （CAPL）, compound action potential amplitude （peak to peak ） （CAPA）, and nerve conduction velocity （NCV） of sciatic-tibial nerve. Serum creatinine （Cre） and urea nitrogen （BUN） concentrations were determined before the first dose on 2nd day （d 2）, d 4, d 8 and d 15 （the day of the first dose as the first day）. RESULTS Compared with normal control group, after colistin sulphate was given for 1 d, Cre showed significant difference （P 〈 0.05 ） ; and for 3 d, BUN and body mass showed significant difference, respectively （ P 〈 0.05 ） ; after colistin sulphate was given for 7 d, the gait and the foot splay showed significant difference （ both P 〈 0.05 ）. Compared with normal control group, after colistin sulphate was given for 1, 3 and 7 d, TI increased by 60%, 60% and 192% （ P 〈 0.01 ）, respectively ; MI increased by 4%, 13% and 100% （P 〈0.05）, respectively; CAPD increased by 15.1%, 11.5% and 52.8% （P 〈 0.05 ）, respectively ; CAPL prolonged by 9.0%, 9.0% and 14.6% （ P 〈 0.05 ）, respectively ; CAPA decreased 0.92%, 16.2% and 47.6% （P 〈0.01 ）, respectively; and NCV decreased by 7.6%, 7.5% and 12.7% （P 〈0.05 ）, respectively. After 7 d of stopping administration, the gait and the foot splay had no significant differences, and all electrophysiology indexes showed a recovery tendency and only CAPA was significantly different （P 〈 0.05 ）. CONCLUTION Nephrotoxicity is earlier than neurotoxicity on mice treated with colistin sulphate, at the same time, the progressive changes in CAP characteristics of the sciatic-tibial nerves are dependent with the time of colistin sulphate administration and abnormal CAPA has the longest duration time.