丹参素抑制乙醛诱导的肝星状细胞T6活化与增殖的研究(英文)  

Danshensu inhibits acetaldehyde-induced proliferation and activation of hepatic stellate cell-T6

作　　者：张莉[1] 吴涛[2] 陈珺明[3] 杨丽丽[1] 宋海燕[1] 季光[1] 

机构地区：[1]上海中医药大学龙华医院脾胃病研究所,上海200032 [2]上海中医药大学中医方证与系统生物学研究中心,上海201203 [3]上海交通大学第六人民医院中医科,上海200233

出　　处：《中西医结合学报》2012年第10期1155-1161,共7页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金资助项目(No.81202979);上海市教育委员会重点学科建设项目(No.J50305,E3008)

摘　　要：目的:研究中药丹参的主要成分丹参素对肝星状细胞(hepatic stellate cell,HSC)活化与增殖的影响。方法:乙醛与HSC-T6共同孵育诱导细胞活化,再分别应用不同浓度的丹参素进行干预。四甲基偶氮唑盐(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT)比色法检测细胞活力,流式细胞术检测细胞周期,实时定量聚合酶链反应法分析细胞Ⅰ型纤溶酶原激活剂抑制物(plasminogen activator inhibitor-1,PAI-1)、转化生长因子β1(transforming growth factor-β1,TGF-β1)、尿激酶型纤溶酶原激活因子(urokinase-type plasminogen activator,uPA)和基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)的基因表达。结果:MTT比色法检测表明丹参素可抑制由200μmol/L乙醛诱导的HSC增殖,流式细胞术分析发现丹参素可使处于S期的细胞数量明显增加(P<0.05)。此外,丹参素还能下调TGF-β1和PAI-1的基因表达,并增加uPA的转录水平(P<0.01),但对MMP-2的表达没有明显影响。结论:丹参素可抑制乙醛诱导的HSC-T6的活化与增殖,并可调节参与细胞外基质沉积的细胞因子的表达。To evaluate the effects of danshensu, the main component of the extract of Chinese medicine Salvia miltiorrhiza, on the proliferation and activation of hepatic stellate cells （HSCs）. METHODS： The activation of HSC-T6 was induced by exposure to acetaldehyde. In the meantime, different doses of danshensu were added to the culture medium. After 24 h of treatment with danshensu in acetaldehyde, the viability of HSC-T6 cells was evaluated by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay, the cell cycle was determined through flow cytometry, and the gene transcription levels of plasminogen activator inhibitor-1 （PAl-1）, transforming growth factor-β1 （TGF-i31）, urokinase-type plasminogen activator （uPA） and matrix metalloproteinase-2 （MMP-2） were analyzed by real-time quantitative polymerase chain reaction. RESULTS： The proliferation of HSCs induced by 200/zmol/L acetaldehyde could be significantly inhibited by danshensu, and the percentage of HSCs in S phase was significantly increased as compared with the control cells （P〈0.05）, which were respectively evidenced by MTT assay and flow cytometry. Danshensu down-regulated the mRNA expression of TGF-β1 and PAl-1 and up-regulated the uPA transcription level （P〈0.01）, while the transcription level of MMP-2 was not significantly affected in HSC-T6. CONCLUSION： Danshensu can inhibit the proliferation and activation of HSC-T6, as well as regulate some cytokines involved in extracellular matrix accumulation, which offers a potential therapeutic alternative for liver fibrosis.

关 键 词：丹参素 肝细胞 细胞增殖 细胞外基质 体外研究 

分 类 号：R575.2[医药卫生—消化系统]