抗氰新药DDD和4-二甲基氨基苯酚对大鼠高铁血红蛋白浓度的影响

目的 通过比较4-二甲基氨基苯酚（4-DMAP）和DDD对大鼠血液高铁血红蛋白（MeHb）浓度的影响,排除DDD形成MeHb的可能性,为该药的安全使用提供试验依据.方法 将大白鼠70只分成两组,分别进行时间-效应试验和量-效试验.时效试验中大鼠分别口服DDD或4-DMAP,于10、30、60min取血样测定MeHb浓度;剂量-效应试验中大鼠口服不同剂量DDD或腹腔注射不同剂量4-DMAP,于30min取血样用铁氰化钾法测定MeHb浓度.结果 时-效试验中,4-DMAP引起大鼠血液MeHb浓度显著升高,DDD不引起MeHb浓度变化,给DDD 10、30、60min后,大鼠血液MeHb分别为2.87±0.32、2.42±0.19、2.56±0.41,给4-DMAP10、30、60min后,大鼠血液MeHb分别为8.62±0.93、22.47±3.67、19.33±4.12,与对照组比较P＜0.05.量效试验中,1、2、3mg/kg的4-DMAP造成大鼠血液MeHb以量效依赖方式升高,大鼠血液MeHb分别为18.54±2.93、22.47±3.67、31.08±4.04,50、100、150mg/kg的DDD不引起大鼠血液MeHb浓度变化,大鼠MeHb分别为2.35±0.44、2.42±0.19、2.71±0.42.结论 4-DMAP是MeHb形成剂,DDD不具备形成MeHb的能力.

Comparative study on new cyanide-resistant DDD and 4-diaminophenol in methylhemoglobin forming ability

Objective To compare the effects of 4-DMAP and DDD on rats blood methylhemoglobin（MeHb）concentrations and reject the possibility that the new drug of DDD could induce the formation of MeHb.Methods 70 rats were divided into 2groups for the time-effect and dose-effect studies.For the time-effect experiment,the rats were administrated with DDD orally or 4-DMAP intraperitonealy at the doses of 100mg/kg and 2mg/kg,respectively,The blood samples were collected at the points of 10,30 and 60min and MeHb concentrations were determined by the method of potassium ferricyanide.For the dose-effect experiment,the rats were administrated with DDD（50,100,150mg/kg）and4-DMAP（1,2,3mg/kg）,Blood samples were collected at 30 min and the MeHb were tested by the same way.Results4-DMAP injection produced different increases of the concentrations of MeHb in the rat blood at different time points,but the concentrations of MeHb in the rats administrated with DDD were not changed.Rat blood MeHb was 2.87±0.32,2.42±0.19,2.56±0.41 after 10,30,60 min with DDD respectively,and rats blood MeHb was 8.62±0.93,22.47±3.67,19.33±4.12 after 10,30,60 min with 4-DMAP respectively（P0.05）.In the dose-effect experiments,4-DMAP（1,2,3mg/kg）induced the increase of MeHb in a dose dependent manner,rats blood MeHb was 18.54±2.93,22.47±3.67,31.08±4.04 respectively.However DDD（50,100,150mg/kg）did not induce any change of MeHb.rats blood MeHb was 2.35±0.44,2.42±0.19,2.71±0.42 respectively.Conclusion 4-DMAP can in duce MeHb formation,but DDD could not.