雷公藤内酯醇的遗传毒性评价

田逸君; 郑怡文; 朱玉平; 张晓芳; 宗英; 陆国才

doi:10.3969/j.issn.1006-0111.2016.03.006

雷公藤内酯醇的遗传毒性评价

doi: 10.3969/j.issn.1006-0111.2016.03.006

第二军医大学卫生毒理学教研室, 上海 200433

基金项目: 国家科技重大专项基金(2014ZX09J14106-06C,13CXZ005,BWS14J023);国家自然科学基金(81473291,81402651);上海市自然科学基金(13ZR144940)

Genotoxicity evaluation of triptolide

Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433, China

摘要: 目的观察雷公藤的主要有效成分之一雷公藤内酯醇的遗传毒性。方法采用鼠伤寒沙门氏菌回复突变试验(Ames试验)、体外培养CHO细胞染色体畸变试验和小鼠骨髓微核试验检测雷公藤内酯醇的遗传毒性。结果 Ames试验提示在每皿1.6~1000 μg受试剂量下,在加或不加S9代谢活化系统时,受试物对组氨酸缺陷型鼠伤寒沙门氏菌TA97、TA98、TA100、TA102及TA1535所诱发的回复突变菌落数均与溶媒对照的突变菌落数相近。体外培养CHO细胞染色体畸变试验结果显示0.01、0.02和0.04 μg/ml 3个剂量的受试物,对加与不加S9代谢活化系统培养的CHO细胞的染色体畸变率无明显影响。小鼠骨髓微核试验设180、360、720 μg/kg 3个剂量,在720 μg/kg剂量时,雷公藤内酯醇有诱发骨髓嗜多染红细胞微核率增高的效应。结论在本实验条件下,雷公藤内酯醇对鼠伤寒沙门氏菌无致突变性,对哺乳动物培养细胞染色体无致畸变作用,720 μg/kg剂量下对ICR小鼠有诱发骨髓嗜多染红细胞微核率增高的效应。提示雷公藤内酯醇对人体可能具有潜在的遗传毒性。
- 雷公藤内酯醇 /
- 致突变试验 /
- 鼠伤寒沙门氏菌回复突变试验 /
- 染色体畸变试验 /
- 微核试验
Abstract: Objective To study the genotoxicity of triptolide, an important active component of Tripterygium wilfordii Hook f. Methods Ames test, in vitro chromosomal aberration test of CHO cell and in vivo micronucleus assay were performed to investigate the genotoxicity of triptolide. Results The Ames test showed that triptolide did not increase mutagenicity for TA97, TA98, TA100, TA102 and TA1535 strains at the dosage of 1.6~1000 μg per plate with and without metabolic activation system S9. Results of in vitro CHO cell chromosomal aberration test indicated that there was no statistical difference between the triptolide groups (doses of 0.01, 0.02 and 0.04 μg/ml) and the solvent control group with and without metabolic activation system S9. However, triptolide significantly increased polychromatophilic erythrocyte micronucleus formation at the dosage of 720 μg/kg in ICR mice. Conclusion Triptolide did not induce genetic toxicity based on the Ames test and chromosomal aberration test, but could increase micronucleus formation at the dosage of 720 μg/kg. These results indicated that triptolide may have potential genotoxicity on human health.
- triptolide /
- mutagenicity test /
- Ames test /
- chromosomal aberration test /
- micronucleus assay

[1]	张晓慧, 杨恩才, 万春平.雷公藤内酯醇及其衍生物的药理作用研究进展[J].云南中医中药杂志,2013,34(8):64-65.
[2]	国家食品药品监督管理总局.药物遗传毒性研究技术指导原则[EB/OL].2007-10-23[2015-11-15].http://www.sda.gov.cn/WS01/CL1616/90936.html.
[3]	周海钧.ICH药品注册的国际技术要求:安全性部分[M].北京:人民卫生出版社,2001:37-61.
[4]	OECD. Test Guidance 471:Bacterial Reverse Mutation Test[S]//OECD Guidance For Testing of Chemicals. Paris:Organization for Economic Cooperation & Development,1997:1-8.
[5]	OECD. Test Guidance 473:In Vitro Mammalian Chromosome Aberration Test[S]//OECD Guidance for Testing of Chemicals. Paris:Organization for Economic Cooperation & Development, 1997:1-7.
[6]	OECD. Test Guidance 474:Mammalian Erythrocyte Micronucleus Test[S]//OECD Guidance for Testing of Chemicals. Paris:Organization for Economic Cooperation & Development,1997:1-7.
[7]	张鹏宇, 张瑞,王雅贤.雷公藤内酯醇抗肿瘤分子机制研究进展[J].中医药学报,2009,37(3):79-82.
[8]	Ling D, Xia H, Park W, et al. pH-sensitive nanoformulated triptolide as a targeted therapeutic strategy for hepatocellular carcinoma[J]. ACS Nano, 2014, 8(8):8027-8039.
[9]	吴娜, 刘星雨,王笃军,等.雷公藤内酯醇对C57BL/6小鼠亚慢性毒性作用的研究[J]. 中成药, 2014,36(5):904-908.
[10]	周顺长, 吴越,王兵,等.雷公藤内酯醇聚合物胶束的急性毒性研究[J].医药导报, 2013, 32(12):1563-1565.
[11]	Qu L, Qu F, Jia Z, et al. Integrated targeted sphingolipidomics and transcriptomics reveal abnormal sphingolipid metabolism as a novel mechanism of the hepatotoxicity and nephrotoxicity of triptolide[J]. J Ethnopharmacol, 2015, 170:28-38.
[12]	骆永伟, 施畅,原野,等.雷公藤甲素的毒理学研究进展[J]. 毒理学杂志, 2009,23(1):74-77.
[13]	Zhang J, Liu L, Mu X, et al. Effect of triptolide on estradiol release from cultured rat granulosa cells[J]. Endocr J, 2012, 59(6):473-481.
[14]	Jin J, Sun XZ, Zhao ZX, et al. Activation of the farnesoid X receptor attenuates triptolide-induced liver toxicity[J]. Phytomedicine, 2015, 22(10):894-901.
[15]	高涛.雷公藤内酯醇靶蛋白及其药理机制研究进展[J].重庆医学,2012,41(35):3777-3780.
[16]	Ho LJ, Chang WL, Chen A, et al. Differential immunomodulatory effects by Tripterygium wilfordii Hook f-derived refined extract PG27 and its purified component PG490(triptolide) in human peripheral blood T cells:potential therapeutics for arthritis and possible mechanisms explaining in part Chinese herbal theory "Junn-Chenn-Zuou-SS"[J]. J Transl Med, 2013, 11:294.
[17]	Ma B, Qi HH, Li J, et al. Triptolide disrupts fatty acids and peroxisome proliferator-activated receptor (PPAR) levels in male mice testes followed by testicular injury:A GC-MS based metabolomics study[J]. Toxicology, 2015, 336:84-95.
[18]	杨建一, 高宝珍,李莉,等.雷公藤多甙对雄性小鼠生殖细胞毒性的研究[J].癌变·畸变·突变,2008,20(5):393-397.

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雷公藤内酯醇的遗传毒性评价

doi: 10.3969/j.issn.1006-0111.2016.03.006

Genotoxicity evaluation of triptolide

计量

雷公藤内酯醇的遗传毒性评价

doi: 10.3969/j.issn.1006-0111.2016.03.006

第二军医大学卫生毒理学教研室, 上海 200433

English Abstract

Genotoxicity evaluation of triptolide

Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433, China

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留言板

雷公藤内酯醇的遗传毒性评价

doi: 10.3969/j.issn.1006-0111.2016.03.006

Genotoxicity evaluation of triptolide

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雷公藤内酯醇的遗传毒性评价

doi: 10.3969/j.issn.1006-0111.2016.03.006

第二军医大学卫生毒理学教研室, 上海 200433

English Abstract

Genotoxicity evaluation of triptolide

Department of Hygiene and Toxicology, Second Military Medical University, Shanghai 200433, China

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