生川乌提取物遗传毒性研究  

GENOTOXIC RESEARCH ON THE EXTRACT OF CRUDE SICHUAN ACONITE ROOT

作　　者：卢豪[1,2,3] 王亚其[1] 潘黎[1,2] 陈红钰[1,2] 何晓娟[1,2] 李宏霞[1] 

机构地区：[1]四川大学华西医院国家成都中药安全性评价中心,成都610041 [2]四川大学华西公共卫生学院 [3]成都军区疾病预防控制中心

出　　处：《现代预防医学》2008年第20期4014-4016,共3页Modern Preventive Medicine

基　　金：国家自然科学基金资助项目(30230410)

摘　　要：[目的]选用目前新药遗传毒性评价中推荐使用的3种试验方法(小鼠骨髓微核试验、鼠伤寒沙门氏菌回复突变试验、体外CHL细胞染色体畸变试验)研究生川乌的遗传毒性。[方法]小鼠骨髓微核试验设3个生川乌提取物给药剂量组(26.0、13.0、6.5g生药/kg)、阴性对照组和阳性对照组(环磷酰胺40mg/kg)。Ames试验选用两种方法:直接法和代谢活化法。试验菌株为鼠伤寒沙门氏组氨酸缺陷型菌株TA97、TA98、TA100、TA102、TA1535,生川乌提取物在试验中设6个剂量组(5.000、2.500、1.250、0.625、0.313、0.156mg生药/皿),同时设自发回复突变对照组、阳性对照组。体外CHL细胞染色体畸变试验也选用两种方法:直接法和代谢活化法。试验设5个生川乌提取物浓度组(5.000、2.500、1.250、0.625、0.313mg生药/ml),阴性对照及阳性对照组。[结果]小鼠骨髓微核试验生川乌提取物各剂量组小鼠骨髓多染红细胞微核率与阴性对照组相比,差异无统计学意义(P﹥0.05)。Ames试验生川乌提取物在加或不加肝微粒体酶(S9)时均未见引起TA97、TA98、TA100、TA102、TA1535试验菌株基因突变,即Ames试验阴性,试验重复一次,所得结论相同。体外CHL细胞染色体畸变试验生川乌提取物在加或不加S9时均未引起CHL细胞的染色体畸变,试验结果为阴性,试验重复1次,所得结论相同。[结论]在本实验室条件下,生川乌提取物在小鼠骨髓微核试验、Ames试验及体外CHL细胞染色体畸变试验中均为阴性结果,故认为在本实验条件下,生川乌提取物无遗传毒性。[Objective] To study the genetoxic of crude Sichuan aconite root by three experimental methods recommended by the evaluation of new drug genetoxic including the Micronuclei assay in mice, Salmonella reverse mutation assay and CHL chromosome aberration assay. [ Methods ] There were 3 dosing groups for the crude Sichuan aconite root in the Micronuclei assay in mice, 26.0, 13.0 and 6.5 g raw drug/kg, with a negative control with distilled water and a positive control with 40 mg/ kg Cyclophosphamide. Salmonella reverse mutation assay adopted two methods including with and without S9 mixture. Test Strains TA97, TA98, TA100, TA102 and TA1535 were used in this study. There were six dose groups for extraction as follows： 5, 2.5, 1.25, 0. 625, 0.313 and 0.156mg raw drug/plate, with a negative control and a positive control. CHL chromo, some aberration assay adopted two methods including with and without S9 mixture. There were 5 doses groups for 5, 2.5, 1.25, 0.625 and 0.313 mg raw drug/ml, with a negative control and a positive control. [Results] The micronuclei rates of mice bone marrow cell in all dosing groups of the extraction did not found significant difference when Compared with the negative control （P 〉 0.05）. The number of revertant colony of dosing groups did not reach to two times of the number corresponding of spontaneous revertant colony. The frequency of chromosome aberration in dosing groups of the extract did not showed significant difference compared with negative control （P 〉 0.05） at the time of 24h and 48h, respectively. [ Conclusion ] There were negative results in the Micronuclci assay in mice, Salmonella reverse mutation assay and CHL chromosome aberration as, say.The results showed the extract of crude Sichuan aconite root has no genotoxicity.

关 键 词：生川乌提取物 遗传毒性 小鼠骨髓微核试验 AMES试验 染色体畸变试验 

分 类 号：R99[医药卫生—毒理学]