丙酮酸乙酯注射液的大鼠长期毒性试验

Long-term toxicity test of ethyl pyruvate injection in rats

目的:观察连续肌肉注射丙酮酸乙酯(ethyl pyruvate,EP)注射液后大鼠产生的长期毒性反应。方法:按年龄、体质量、性别均衡的原则将60只SD大鼠随机分成EP注射液高(2 400 mg/kg)、中(1 600 mg/kg)、低(50 mg/kg)剂量组和溶剂对照组,每组15只,3个给药组每天进行双后肢(或臀部)肌肉注射给药,连续14 d,溶剂对照组则给予等容量大豆油,观测大鼠一般情况、血常规、血液生物化学等相关毒性反应指标的变化。结果:大鼠每次注射EP药物后5 min内高剂量组产生明显抽搐、俯卧、后肢僵直、呼吸急促等毒性反应但逐渐缓解,注射后30 min内即恢复正常,未见动物死亡;中剂量组上述毒性反应较轻;低剂量组与溶剂对照组无明显差别。血常规和血液生物化学相关指标除在第1次给药14 d后高剂量组的肺和脾系数,中剂量组脾系数明显增加外(P<0.05),其余各剂量组与溶剂对照组比较差异均无统计学意义(P>0.05),停药后各剂量组均未见迟缓性毒性发生。结论:高剂量(2 400 mg/kg)EP注射液对大鼠中枢神经系统会产生较明显毒性作用,但为可逆性的。EP注射液作为单次用药对大鼠无长期毒性作用。

OBJECTIVE： To investigate the toxicity on target organ after continuous intramuscular injection of ethyl pyruvate injection. METHODS： The high, medium and low dose groups and solvent control group were set up, according to the age, weight and gender. Each group had 15 animals. EP injections were given intramuscularly at 2 400, 1 600, 50 mg/kg, and equal volume of solvent in hindlimbs or buttocks for 14 days. We measured blood indicators and documented the extent of EP toxicity in rats. RESULTS ： 14 days after EP injection all animals survived.