藤甲酰苷的急性毒性、遗传毒性和生殖毒性  

Study on acute toxicity, genetoxicity and reproductive toxicity( the second stage of the rat) of garcinia glycosides

作　　者：纪圣君[1] 刘晶[1] 邓晶晶[1] 李文军[1] 金英[2] 韩爽[3] 刘举[1] 周云鹏[1] 徐利锋[1] 王洋[1] 陈烨[1] 

机构地区：[1]辽宁大学药学院辽宁省新药研发重点实验室,辽宁沈阳110036 [2]沈阳兴齐眼药股份有限公司,辽宁沈阳110024 [3]辽宁省肿瘤医院,辽宁沈阳110042

出　　处：《中国新药与临床杂志》2014年第10期729-734,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家“十一五”规划“重大新药创制”重大科技专项资助项目(2009ZX09103-030);辽宁大学“211工程”三期建设重点资助项目

摘　　要：目的研究藤甲酰苷的急性毒性、遗传毒性和大鼠Ⅱ阶段的生殖毒性。方法急性毒性实验采用Bliss法,通过300、250、100、50、25 mg·kg^-1五个剂量组测定昆明小鼠半数致死量;遗传毒性设置Ames实验和微核实验,其中Ames实验采用平板掺入法,设置500、100、20、4、0.8μg五个剂量组,小鼠微核试验设65、32.5、16.25 mg·kg^-1三个剂量组;生殖毒性实验通过43、8.7、4.35 mg·kg^-1三个剂量组考察大鼠致畸情况。结果藤甲酰苷对小鼠半数致死量为129.77 mg·kg^-1,其95%可信限为93.289-179.38 mg·kg^-1;Ames实验中受试物各剂量组回变菌落数均未超过生理盐水组2倍,且无剂量-反应关系;微核试验与生理盐水组之间无显著差异,结果均为阴性;致畸实验与生理盐水组相比,8.7和4.35 mg·kg^-1剂量组对大鼠的胚胎形成、胎鼠的发育、骨骼及内脏无明显影响（P〉0.05）,43 mg·kg^-1剂量组有显著差异（P〈0.05）。结论藤甲酰苷属中等毒性化合物,在本实验剂量范围内藤甲酰苷不具有遗传毒性。8.7和4.35 mg·kg^-1剂量组无致畸胎毒性,而43 mg·kg^-1剂量组有一定的致畸毒性。AIM To study the acute toxicity, genetoxicity and reproductive toxicity（the second stage of the rat） of Garcinia glycosides. METHODS Acute toxicity test was performed by Bliss method, and lethal dose50（ LD50） of KM mice was determined by 300, 250, 50, 25 mg·kg-1five doses. Genetoxicity test included Ames test and micronucleus test. The former was performed by 500, 100, 20, 4, 0.8 μg five doses, the latter by 65, 32.5, 16.25 mg·kg-1three doses. 43, 8.7, 4.35 mg·kg-1three doses were used in teratogenicity test.RESULTS LD50 of garcinia glycosides in mice was 129.77 mg·kg-1, with the 95% confidence interval of 93.289-179.38 mg·kg-1. The colony number of return mutant in five doses was two times less than the physiological saline control group, no dose- responserelationship in the Ames test. The marrow micronucleus in three dose groups was not significantly higher than that of the control group. The results were negative. Compared with saline control group, 8.7 和 4.35 mg·kg-1 two doses group were no obvious effect（ P〈0.05） on embryogenesis,growth and concentrations, bones and internal organs, the group of higher dosage（ 43 mg·kg-1） was obvious（P〈0.05）. CONCLUSION Garcinia glycosides was in middle- toxic class, no inheritance toxicity was found in this paper. The 8.7 和 4.35 mg·kg-1 two doses groups were no teratogenic toxicity, but there was teratogenic toxicity in the 43 mg·kg-1dose group.

关 键 词：藤甲酰苷 半数致死量 诱变力试验 AMES试验 微核试验 致畸作用 

分 类 号：R965.2[医药卫生—药理学]