方法8周龄雄性Wistar大鼠32只，随机分为A、B、C、D 4组，每组8只。A组为对照组；B组给予100 mg/kg头孢曲松腹腔注射；C组给予150 mg/kg头孢曲松腹腔注射；D组给予200 mg/kg头孢曲松腹腔注射。给药时间为10 d。分别收集给药前1 d和处死前1 d大鼠的24 h尿液，行生化分析和草酸测定。处死各组大鼠后采集大鼠血标本行生化分析，切取大鼠肾脏，观察肾脏变化及肾盂内成石，肾组织行Von Kossa染色，观察肾实质内含钙结晶。比较各组大鼠肾脏重量、肾脏成石以及24 h尿和血生化指标的差异。
结果对照组大鼠肾脏未见结石形成，Von Kossa染色未见黑色含钙结晶颗粒。实验组大鼠肾脏均无肉眼可见结石形成。100 mg/kg头孢曲松实验组中，有4只大鼠（50.0%，4/8）可见Von Kossa染色阳性；150 mg/kg头孢曲松实验组中有5只大鼠（62.5%，5/8）可见Von Kossa染色阳性；200 mg/kg头孢曲松实验组中有5只大鼠（62.5%，5/8）可见Von Kossa染色阳性。其中150 mg/kg及200 mg/kg头孢曲松组各有1只大鼠（12.5%，1/8）肾脏切片Von Kossa染色可见大量含钙结晶。150 mg/kg头孢曲松组24 h尿钙排泄量较对照组明显增加，差异有统计学意义（P＝0.047），经计算得出尿中钙/肌酐（uCa/Cr）比值，150 mg/kg头孢曲松组较对照组明显升高，差异有统计学意义（P＝0.016）。
Animal ModelEstablishment of rat model of ceftriaxone associated urolithiasis
Zhang Xin, Xiao Bo, Huang Xiaobo, Chen Song, Li Jianxing, Hu Weiguo, Wang Shu
Cite as Chin J Exp Surg, 2017,34（10）： 1789-1791. DOI： 10.3760/cma.j.issn.1001-9030.2017.10.052
To establish a rat model of ceftriaxone associated urolithiasis and investigate the possible mechanism of its formation.
Thirty-two male Wistar rats aged 8 weeks were randomly divided to four groups： group A served as control group; groups B, C and D received ceftriaxone sodium for 10 days with dosage of 100, 150 and 200 mg/kg, respectively. The 24-h urine was gathered before intraperitoneal injection was conducted and before the end of experiment for the determination of oxalate and biochemical analysis. All rats were sacrificed with over-dose of carbon dioxide. The blood was collected for biochemical analysis. Kidneys were collected to observe the urinary stone formation and for Von Kossa staining. All the data were processed with the statistical software of SPSS 16.0.
There were no visible calculi in these four groups, however, Von Kossa stains were positive in the three experimental groups, with the incidence of 50.0% （4/8） in group B, 62.5% （5/8） in group C and 62.5% （5/8） in group D. The incidence of massive calcium crystal deposits was 12.5% （1/8） in group C and 12.5% （1/8） in group D. No significant differences were observed in the incidences of calcium crystal deposits in groups with different dosages. Both the 24-h urinary excretion of calcium and uCa/Cr ratio in the 150 mg/kg group were increased markedly as compared with the control group.
Ceftriaxone could induce the formation of crystals in the kidney of rats. Ceftriaxone has the potential to significantly increase urinary excretion of calcium, which may be responsible for ceftriaxone associated urolithiasis.
Chinese Journal of Experimental Surgery