蛋白组学技术在中药肝毒性中的应用

中国药物警戒 ›› 2015, Vol. 12 ›› Issue (5): 282-285.

蛋白组学技术在中药肝毒性中的应用

李晓宇¹,黄娜娜^1,2,孙蓉^1*

1.山东省中医药研究院，山东济南 250014;
2.山东中医药大学，山东济南 250355

收稿日期:2015-03-31 发布日期:2015-06-08
通讯作者: 孙蓉，女，博士，研究员·博导，中药药理与毒理。
作者简介:李晓宇，女，研究实习员，中药药理与毒理。

Application of the Technology of Proteomics in Hepatotoxicity of TCM

LI Xiao-yu¹ ,HUANG Na -na^1,2 ,SUN Rong¹

1.Shandong Academy of Chinese Medicine, Shandong Jinan 250014, China;
2.Shandong University of Traditional Chinese Medicine, Shandong Jinan 250014, China

Received:2015-03-31 Published:2015-06-08
Supported by:
国家自然科学基金面上项目（81374059）；山东省自主创新和成果转化项目（2014ZZCX02104）；山东省自然基金重点项目（2011ZRB14333）。

摘要/Abstract

摘要： 目的讨论蛋白组学研究技术在中药肝毒性中的最新应用进展。方法对国内外文献进行搜集、整理和归纳，研究近年来蛋白组学技术对中药肝毒性的应用概况。结果与传统毒理学研究技术相比，蛋白组学尤其是毒理蛋白质组学整合了经典毒理学、病理学和蛋白质差异表达分析技术，可在离体水平上更快、更准确地发现毒性物质，并用于寻找潜在的生物标记物和毒靶研究，也可应用于机制研究的补充和验证。结论蛋白组学技术提升了中药肝毒机制的认知水平，为中药肝毒性的毒性蛋白标志物的筛选、毒性机制研究、毒性预测与毒性蛋白质数据库的建立等方面奠定了技术可行性，进而为中药肝毒性的评价、机制研究、临床诊断领域提供了一个适宜技术体系。

关键词: 蛋白组学, 中药肝毒性, 毒理学

Abstract: Objective To discuss the latest progress of proteomics technology in hepatotoxicity of traditional Chinese medicine (TCM). Methods References in the last decade at home and abroad about the application of proteomics technology in hepatotoxicity of TCM were collated, analyzed and summarized. Results Compared with traditional toxicology, to xicoproteomics was used to find out the toxic substances more quickly and accurately when classic toxicology, pathology and proteins express analysis technology were integrated into it, which could be applied to the study of biomarkers and drug targets independently and also to the supplement and verification of the mechanism research. Conclusion The knowledge of toxic mechanism of TCM has been raised to a new level due to the application of technology of proteomics, which is a suitable platform for screening toxicity biomarkers, exploring mechanism of toxic effect predicting toxicity and establishing protein databases related to toxic effects, and provides an appropriate technology system for the research of hepatotoxicity assessment, clinical diagnosis and hepatotoxicity mechanism of TCM.

Key words: proteomics, hepatotoxicity of TCM, toxicology

中图分类号:

李晓宇,黄娜娜,孙蓉. 蛋白组学技术在中药肝毒性中的应用[J]. 中国药物警戒, 2015, 12(5): 282-285.

LI Xiao-yu ,HUANG Na -na ,SUN Rong. Application of the Technology of Proteomics in Hepatotoxicity of TCM[J]. Chinese Journal of Pharmacovigilance, 2015, 12(5): 282-285.

参考文献

[1] Larrey D. Epidemiology and individual susceptibility to ad-verse drug reactionsaffecting theliver[J].Seminarsin Liver Disease,2002,22 (2):145-155.
[2]侯凤琴,霍娜,刘霞,等.慢性药物性肝损伤 33例临床特点分析[J].中国实用内科杂志,2011,31(12):941-943.
[3] WasingerV C, Cordwell S J, Cerpa-Poljak A, et al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis, 1995, 16(1): 1090-1094.
[4] Tyers M, Mann M. From genomics to proteomics[J]. Nature, 2003, 422(6928): 193-197.
[5] Fountoulakis M, JuranvilleJ F, Berndt P, et al. Two-dimensional database of mouse liver proteins. An update[J]. Electrophoresis, 2001, 22(9): 1747-1763.
[6] 范冬梅,杨铭.双向凝胶电泳 -蛋白质组分析的核心技术[J].中国生化药物杂志,2005,26(3):182-184.
[7] Langen H, Takács B, Evers S, et al. Two dimensional map of the proteome of Haemophilus influenzae[J]. Electrophoresis, 2000, 21 (2): 411-429.
[8] O'FarrellP H. High resolution two-dimensional electrophoresis of proteins[J].Journalofbiologicalchemistry,1975,250(10): 4007-4021.
[9] LiottaL A, Ferrari M, Petricoin E. Clinical proteomics: written in blood[J]. Nature, 2003, 425(6961): 905-905.
[10]桑志红,杨松成.电喷雾电离质谱及其在蛋白质化学研究中的应用[J].国外医学.药学分册,2000,27(1):38.
[11] Arredouani M, Matthijs P, Van Hoeyveld E, et al. Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release[J]. Immunology, 2003, 108(2): 144-151.
[12]王莹,王全军,廖明阳.蛋白质组学技术在药物肝毒性研究中的应用[J].中国新药杂志,2008,17(4):348-352.
[13] Geiss K, Hussain S, Juhl M J, et al. Proteomic evaluation of cell preparation methods in primary hepatocyte cell culture [J]. Electrophoresis, 2002, 23: 2223-2232.
[14] Gao J, Garulacan L A, Storm S M, et al. Identification of in vitro protein biomarkers of idiosyncratic liver toxicity[J]. Toxicology in vitro, 2004, 18(4): 533-541.
[15] Kumagai K, Ando Y, Kiyosawa N, et al. Toxicoproteomic inves-tigation of the molecular mechanisms of cycloheximide-induced hepatocellular apoptosis in rat liver[J]. Toxicology, 2006, 228(2): 299-309.
[16] Kling P, F orlin L. Proteomic studies in zebrafish liver cells ex-posed to the brominated flame retardants HBCD and TBBPA [J]. Ecotoxicology and environmental safety, 2009, 72(7): 1985-1993.
[17] Zgoda V, Tikhonova O, Viglinskaya A, et al. Proteomic profiles of induced hepatotoxicity at the subcellular level[J]. Proteomics, 2006, 6(16): 4662-4670.
[18] Eng J K, HowellK E. Proteomics of rat liver Golgi complex: minor proteins are identified through sequential fractionation[J]. Electro-phoresis, 2000, 21: 3441-3459.
[19]邓敬桓.SELDI蛋白芯片技术筛选 HBsAg携带者和肝硬化患者血清蛋白标记物的研究[D].广西医科大学,2008.
[20]孙强玲,刘银坤,卢雯静,等.人健康肝组织刀豆凝集素(ConA)结合型糖蛋白组学研究[J].中国科学:C辑,2007,36(6):543-551.
[21] Yamamoto T, Kikkawa R, Yamada H, et al. Investigation of pro-teomic biomarkers in in vivo hepatotoxicity study of rat liver: toxicity differentiation in hepatotoxicants[J]. The Journal of toxi-cological sciences, 2006, 31(1): 49-60.
[22]卢春凤,陈廷玉,赵锦程,等.槲皮素对 INH诱导的大鼠肝损伤及肝组织 Bcl-2和 Bax表达的影响[J].解剖学研究,2010(1):28-31.
[23]刘小转,李三强,任江涛,等.HSP70,IL-6和 TNF-OL在 CCl4诱导的小鼠急性肝损伤组织中的表达及意义[J].山东医药,2011,51 (35):17-19.
[22]赵荣华.肝郁 -脾虚 -肝郁脾虚证与疏肝健脾方关系的肝脏蛋白组学研究[D].北京中医药大学,2014.