喜马拉雅旱獭作为药物线粒体毒性替代模型的可行性分析

doi:10.3969/j.issn.1674-5817.2012.05.014

实验动物与比较医学 ›› 2012, Vol. 32 ›› Issue (5): 436-440.DOI: 10.3969/j.issn.1674-5817.2012.05.014

喜马拉雅旱獭作为药物线粒体毒性替代模型的可行性分析

张评浒¹, 陶元清², 江振洲³, 王忠东², 范薇², 张陆勇¹

1.中国药科大学江苏省新药筛选中心, 南京 210009;
2.青海省地方病预防控制所实验动物中心, 西宁 811602;
3.国家新药筛选实验室, 南京 210009

收稿日期:2012-06-12 出版日期:2012-10-25 发布日期:2012-10-25
作者简介:张评浒(1976-),男,博士,副研究员,药理学,E-mail:zhangpinghu@163.com
基金资助:
中央高校基本科研业务费专项资金资助(JKZ2011006)

Feasibility Analysis of Himalayana Marmot as an Alternative Model of Drug Mitochondrial Toxicity Evaluation

ZHANG Ping-hu¹, TAO Yuan-qing², JIANG Zhen-zhou³, WANG Zhong-dong², FAN Wei², ZHANG Lu-yong¹

1. Jiangsu Center for New Drug Screening, China Pharmaceutical University, Nanjing, 210009;
2. Experimental Animal Center of Endemic Prevention and Control Department of Qinghai, Xining 811602,China;
3. National New Drug Screening Lab, China Pharmaceutical University, Nanjing 210009, China

Received:2012-06-12 Online:2012-10-25 Published:2012-10-25

摘要/Abstract

摘要： 目的为了探讨我国青藏高原喜马拉雅旱獭是否可以作为核苷类药物线粒体毒性评价替代模型,本研究从旱獭的系统进化关系对喜马拉雅旱獭在旱獭属中的系统分类地位进行了比较分析。方法以线粒体细胞色素b(Cytb)基因作为遗传进化分析的分子标记,对我国青藏高原喜马拉雅旱獭的Cytb进行了序列测定, 并结合已有的旱獭Cytb基因序列对所有旱獭属的种群进行了系统进化分析。结果喜马拉雅旱獭Cytb基因长1 140 bp, 碱基A、T、C、G的平均含量分别为33.2%、25.4%、28.8%、12.6%。Cytb基因表现出很强的碱基组成偏向性,即在A、T、G、C四种碱基中,G的含量明显低于其他三种碱基的含量。旱獭的Cytb基因的氨基酸使用频率具有一定的偏向性,亮氨酸(Leu)和异亮氨酸(Ile)的使用频率最高,分别为15.69%和11.87%,而半胱氨酸(Cys)使用频率最低为1.08%。与其它旱獭相比,喜马拉雅异亮氨酸(Ile)和半胱氨酸(Cys)的使用频率分别为1.32%和11.87%。系统进化分析结果表明我国喜马拉雅旱獭(M.himalyana)、蒙古旱獭(M.sibirica)、灰旱獭(M.caudata)和红旱獭(M.bobak)与北美旱獭(Woodchuck)属于同一进化组群(置信度为100)。结论喜马拉雅旱獭与美洲旱獭具有较近的亲缘进化关系,属同一组群进化而来,这为寻找新型的核苷类药物线粒体毒性评价替代实验动物模型提供了理论依据。

关键词: 喜马拉雅旱獭, 线粒体, 细胞色素b基因, 系统进化

Abstract: Objective To explore whether Marmots himalayana could replace woodchuck as an alternative model for evaluating the toxicity of nucleotide analogue drugs, the phylogenetic relation of Marmots himalayana with other Marmots were analyzed based on a molecular marker, mitochondrial cytochrome b (Cytb) gene. Methods Cytb genes from Marmots himalayana were sequenced and phylogenetic analysis were performed combined with existing Marmots Cytb gene sequences. Results The Cytb gene of Marmots himalayana was composed of 1140bp nucleotides, in which the average content of A, T, C and G was 33.2%, 25.4%, 28.8%, 12.6% respectively. Significant nucleotides and amino acids bias in Marmots Cytb genes were found: the content of G was significantly lower than that of A, T and C, the usage frequencies of leucine (Leu) and isoleucine (Ile) (11.87% and 15.69% respectively) were significantly higher than that of cysteine (Cys) (1.08%) in all marmots. However, the usage frequencies of isoleucine (Ile, 11.87%) and cysteine (Cys, 1.32%) in Cytb gene of Marmots himalayana from Qinghai-Tibet Plateau were significantly higher than that of other Marmotas. Phylogenetic analysis showed that Chinese M.himalayana, M.sibirica, M.caudata and M.bobak has a close genetic relationship with North America Marmots (Woodchuck), suggesting they were originated from the same species group.Conclusion A close genetic relationship was found between Marmots Himalayana and woodchuck, which provide new evidence for establishing an alternative model for evaluating nucleotide analogue drugs using Marmots Himalayana.

Key words: Marmota Himalayana, Mitochondria, Cytochrome b gene, Phylogeny

中图分类号:

Q959Q95-33

张评浒, 陶元清, 江振洲, 王忠东, 范薇, 张陆勇. 喜马拉雅旱獭作为药物线粒体毒性替代模型的可行性分析[J]. 实验动物与比较医学, 2012, 32(5): 436-440.

ZHANG Ping-hu, TAO Yuan-qing, JIANG Zhen-zhou, WANG Zhong-dong, FAN Wei, ZHANG Lu-yong. Feasibility Analysis of Himalayana Marmot as an Alternative Model of Drug Mitochondrial Toxicity Evaluation[J]. Laboratory Animal and Comparative Medicine, 2012, 32(5): 436-440.

参考文献

[1] 孟德荣. 我国旱獭的种类及国内分布研究[J]. 毛皮动物饲养, 1996(3):18-19.
[2] Steppan SJ, Akhverdyan MR, Lyapunova EA, et al.Molecular phylogeny of the Marmots (Rodentia: Sciuridae): tests of evolutionary and biogeographic hypotheses[J]. Syst Biol 1999, 48(4):715-734.
[3] 陶元清,王忠东.喜马拉雅旱獭实验动物化研究初报[C]. 中国实验动物学会第七届学术年会论文集. 2006, 73-77.
[4] Ellerman JR, Morrison-scott TCS. Checklist of Palaearctic and Indian mammals1758-1946[M]. British Museum (Natural History), 1951.London.
[5] Rausch, RL.On the status of some arctic mammals[J]. Arctic,1953, 6:91-148.
[6] Hall ER, Kelson KR.The mammals of North America[M]. New York:Ronald Press, 1959.
[7] Howell AH.Revision of American marmots[J]. North Am Fauna, 1915, 37:1-80.
[8] Ognev SI.Zveri SSSR i prilezhashchikh stran {Mammals of the USSR and adjacent countries}, Volume 5. Gryzuny {Rodents}[M]. Academy of Sciences of the USSR, Moscow. 1947.
[9] Gromov IM, Bibikov DI, Kalabukov NI and Meier MN. Fauna SSSR. Mlekopitayushchie, 1965 Volume 3, no. 2. Nazemnye Belich’i (Marmotinae) {Fauna of the USSR. Mammals, Volume 3, no. 2.Ground Squirrels (Marmotinae)}[M]. Nauka, Moscow.
[10] Hoffmann RS and Nadler CF. Chromosomes and systematics of some North American species of the genus Marmota (Rodentia: Sciuridae)[J]. Experientia, 1968, 24:740-742.
[11] Richardson FC,Tennant BC,Meyer DJ, et al.An evaluation of the toxicities of 2?Fluorouridine and 2’-Fluorocytidine-HCl in F344 rats and Woodchucks(Marmota monax). Toxicologic pathology, 1999, 27(6):607-617.
[12] Helm Bychowski K and Cracraft J. Recovering phylogenetic signal from DNA sequences: relationships within the corvine assemblage (class aves) as inferred from complete sequences of the mitochondrial DNA cytochrome b gene[J]. Mol Biol Evol, 1993, 10:1196-1214.
[13] Irwin DM, Kocher TD, Wilson AC.Evolution of the cytochrome b gene of mammals[J]. J Mol Evol, 1991, 32:128-144.

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喜马拉雅旱獭作为药物线粒体毒性替代模型的可行性分析

Feasibility Analysis of Himalayana Marmot as an Alternative Model of Drug Mitochondrial Toxicity Evaluation

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