6种黄酮类化合物拮抗肝细胞毒性作用的比较  

Comparison in protective effects of six flavonoids against hepatotoxins-induced cytotoxicity

作　　者：杨阳[1,2] 周桂琼[2] 王再勇[2] 季莉莉[2] 王峥涛[1,2] 

机构地区：[1]中国药科大学生药研究室,江苏南京211198 [2]准化教育部重点实验室、中药新资源与质量标准综合评价国家中医药管理局重点研究室,上海201210

出　　处：《中国新药与临床杂志》2011年第4期289-293,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学青年基金(30801544);上海市科技启明星计划(跟踪)(10QH1402200);上海市教委科研创新项目(09ZZ125);“重大新药创制”科技重大专项(2009ZX09052-024)

摘　　要：目的观察芹菜素、木犀草素、白杨素、高良姜素、山奈酚、黄芩素6种结构相近的黄酮类化合物对肝毒性物质诱导的人正常肝细胞株L-02细胞及小鼠原代肝细胞损伤的保护作用,并对其保护肝细胞损伤活性的强弱进行比较及结构分析。方法培养的L-02细胞及小鼠原代肝细胞分别给予10mmol·L^(-1)四氯化碳(CCl_4)、500μmol·L^(-1)牛磺酸脱氧胆酸(TDCA)、2μmol·L^(-1)川楝素(toosendanin,TSN)和25μmol·L^(-1)千里光碱(senecionine,SENE)诱导细胞凋亡。6种黄酮类化合物(100μmol·L^(-1))分别与细胞预孵15min后,加入肝毒性物质,48h后MTT法检测细胞存活率。结果与空白对照组相比,4种肝毒性药物都能明显降低肝细胞的存活率(P<0.01)。黄酮类化合物处理后,黄芩素和山奈酚能不同程度地提高肝细胞损伤模型组的细胞存活率(P<0.01)。其他4种黄酮类化合物对肝细胞存活率无显著作用。结论黄芩素和山奈酚具有抑制肝毒性物质诱导的L-02细胞和小鼠原代肝细胞毒性的作用,有潜在的抗氧化保肝活性,而芹菜素、木犀草素、白杨素、高良姜素无明显的拮抗肝毒性作用。AIM To observe the protective effects of apigenin,luteolin,chrysin,galangin,kaemp-ferol and baicalein present study is designed of six flavonoids with similar structure against hepatotoxicity in human L-02 cells and mouse primary hepatocytes,and explore the relationship between their structures and actions.METHODS The cultured human L-02 cells and mouse primary hepatocytes were treated with carbon tetrachloride（CC1_4,10mmol·L^（-1））,toosendanin（TSN,2μmol·L^（-1））,senecionine（SENE,25μmo·L^（-1）） and deoxycholic acid taurine（TDCA,500μmol·L^（-1））,respectively.The hepatotoxins were added after flavonoids（100μmol·L^（-1）） were preincubated with the cells for 15 min.MTT assay was used to detect the cell viability after the incubation for 48 h.RESULTS Four hepatotoxins could siginificantly reduce the cell viability （P0.01） compared with the control group.After the treatments,baicalein and kaempferol could increase the cell viability of hepatotoxins-treated hepatocytes（P0.01）.However,other compounds had no protective effects against hepatotoxicity.CONCLUSION Baicalein and kaempferol could both significantly prevent these hepatotoxins-induced cytotoxicity in human L-02 cells and mouse primary hepatocytes,however,apigenin, luteolin,chrysin and galangin failed to do so.

关 键 词：黄酮类 肝毒性 肝细胞 芹菜素 木犀草素 白杨素 高良姜素 山奈酚 黄芩素 

分 类 号：R965[医药卫生—药理学]