丹参注射液单次给药的毒性及遗传毒性研究

目的研究丹参注射液的单次给药毒性及遗传毒性,为评价其安全性提供毒理学依据。方法采用一次性给予丹参注射液,观察ICR小鼠产生的毒性反应;用体外细菌回复突变(Ames)实验、中国仓鼠肺成纤维细胞(CHL)体外染色体畸变实验、小鼠骨髓嗜多染红细胞微核实验进行丹参注射液的遗传毒性研究。结果在单次给药毒性中,5个剂量组动物死亡数分别为9,7,4,3和0只;Ames实验中,丹参注射液剂量分别为5 000,2 000,500,50和5μg·皿-1,无论加或不加哺乳动物肝脏微粒体酶(S9),各剂量组的回复突变菌落数均未出现剂量依赖性的增加,结果为阴性;在染色体畸变实验中,非活化条件或代谢活化条件下,细胞的染色体畸变率均未出现剂量依赖性增加;在微核实验中,与溶媒对照组比较,丹参注射液各剂量组中的微核率均无显著性差异。结论在本实验条件下,单次给药毒性研究中,丹参注射液小鼠静脉注射给药的LD50为68.72g·kg-1,95%可信限为66.92~70.58g·kg-1,其对小鼠的急性毒性可能靶器官组织为肺脏。遗传毒性实验结果均为阴性,即中药制剂丹参注射液无潜在的致突变性。

Study of toxicity and genotoxicity of Danshen Injections single drug administration

Objective To evaluate the toxicity and genotoxicity of Danshen (Salvia miltiorrhiza) Injections single drug administration.Methods ICR mice were tested to observe the toxic reactions.Three types of tests were performed:Ames test,CHL chromosome aberration assay,and mouse bone marrow micronucleus test.Results In the single drug toxicity test,animal death numbers were 9,7,4,3,0 for five dosage group respectively.In the Ames test,with mammalina liver microsomal enzymes (S9) or without S9,Danshen Injections in 5 000,2 000,500,50 and 5 μg·dish-1 dose range for five bacteria showed no dose-dependent increase.In the chromosome aberration test,under the non-activation conditions or metabolic activation conditions,the cell chromosome aberration showed no dose-dependent increase.In the micronucleus test,there was no statistically significant difference between each dose group and the solvent control group.Conclusion Under the conditions of the test,the LD50 of Danshen Injections given in drops intravenously in mice was 68.72 g·kg-1,on 95% confidence limit, 66.92-70.58 g·kg-1.Lung tissue maybe the acute toxicity target organ.The genotoxicity tests were negative,namely,Danshen Injections showed no mutagenic effect in this test.