| 血清微小RNA在中药肝毒性临床前评价中的应用研究 |
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| 引用本文： | 苏钰文,江振洲,邢同岳,宋聿明,王欣之,王玉荣,吴美娟,张云,王佳颖,王涛,张陆勇.血清微小RNA在中药肝毒性临床前评价中的应用研究[J].扬州大学学报(农业与生命科学版),2012(2):11-17. |
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| 作者姓名： | 苏钰文 江振洲 邢同岳 宋聿明 王欣之 王玉荣 吴美娟 张云 王佳颖 王涛 张陆勇 |
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| 作者单位： | 中国药科大学江苏省新药筛选中心;中国药科大学药物质量与安全预警教育部重点实验室;中国药科大学江苏省药效研究与评价服务中心 |
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| 基金项目： | 国家“十一五”科技重大专项(2009ZX09302-002);国家中医药行业科研专项(200707008);江苏省自然科学基金资助项目(BK2011631) |
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| 摘 要： | 通过对19种具有潜在肝脏毒性的中草药进行临床前安全性评价,在观测体重、摄食量、血清生化指标、脏器系数与肝脏组织病理学改变的同时,探讨血清微小RNA(miRNA)作为新型候选标志物在中草药肝损伤诊断中的应用价值。结果表明:与溶剂对照组相比,血清miRNA-122水平显著升高的给药组有6组,而血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平显著升高的分别为2组和3组,其中五倍子组表现为急性药源性肝损伤。在血清miRNA-122的时间相关性和剂量相关性分析中,与血清ALT和AST相比,血清miRNA-122呈现出更高的敏感性,表现为更早期和更大幅度的显著升高。说明血清miRNA-122可作为中草药肝损伤的新型候选诊断标志物,与肝脏组织病理学改变具有良好的相关性,且较传统血清生化学指标更为敏感。
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| 关 键 词： | 中草药 药源性肝损伤 药物安全性评价 生物标志物 微小RNA |
Study on the application of serum microRNA in preclinical evaluation for hepatotoxicity induced by herbal medicines |
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| SU Yu-wen,JIANG Zhen-zhou,XING Tong-yue,SONG Yu-ming,WANG Xin-zhi,WANG Yu-rong,WU Mei-juan,ZHANG Yun,WANG Jia-ying,WANG Tao,ZHANG Lu-yong.Study on the application of serum microRNA in preclinical evaluation for hepatotoxicity induced by herbal medicines[J].Journal of Yangzhou University:Agricultural and Life Science Edition,2012(2):11-17. |
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| Authors: | SU Yu-wen JIANG Zhen-zhou XING Tong-yue SONG Yu-ming WANG Xin-zhi WANG Yu-rong WU Mei-juan ZHANG Yun WANG Jia-ying WANG Tao ZHANG Lu-yong |
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| Institution: | 1,2,3(1.Jiangsu Cen of Drug Scr,China Pharm Univ,Nanjing 210009,China; 2.Key Lab of Drug Qual Cont and Pharmacovig,MOE,China Pharm Univ,Nanjing 210009,China; 3.Jiangsu Cen for Pharm Ynamics Res and Eval,China Pharm Univ,Nanjing 210009,China.) |
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| Abstract: | The diagnostic value of serum miRNA-122,which severs as a novel candidate biomarker for herb-induced liver injury,was studied through a preclinical safety evaluation on 19 potential hepatotoxic herbal medicines.In the meanwhile,parameters including body weight,food intake,blood chemistry indicators,organ-to-body-weight ratio and histopathological changes were also observed in this evaluation.The results showed that,by comparison with the vehicle group,serum miRNA-122 significantly elevated in 6 treatment groups,while serum ALT and AST significantly elevated in 2 and 3 treatment groups,respectively.Among the herbs tested,Calla Chinensis could induce acute liver injuries.In time-and dose-related analysis,serum miRNA-122 displayed better sensitivity with the characteristics of earlier appearance and larger fold change than serum ALT and AST.This study demonstrates that serum miRNA-122,which severs as a novel candidate biomarker for herb-induced liver injury,is correlated well with the results of histomorphologic examinations and is much more sensitive than conventional blood chemistry indicators. |
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| Keywords: | herbal medicine drug-induced liver injury drug safety evaluation biomarker microRNA |
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