Danshensu inhibits acetaldehyde-induced proliferation and activation of hepatic stellate cell-T6.
Danshensu inhibits acetaldehyde-induced proliferation and activation of hepatic stellate cell-T6.
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DOI：
10.3736/jcim20121013
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发表时间：
2012-10
期刊：
影响因子：
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通讯作者：
Li Zhang;Tao Wu;Jun-ming Chen;Lili Yang;Haiyan Song;G. Ji
中科院分区：
文献类型：
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作者：
Li Zhang;Tao Wu;Jun-ming Chen;Lili Yang;Haiyan Song;G. Ji
目的观察丹参提取物的主要成分丹参素对肝星状细胞增殖和活化的影响。方法乙醛诱导HSC-T6活化;同时在培养基中加入不同剂量的丹参素。在用乙醛中的丹参素处理24小时后，通过3-羟色胺法评价HSC-T6细胞的活力。MTT法检测细胞增殖，流式细胞仪检测细胞周期，流式细胞仪检测纤溶酶原激活物抑制剂-1（派-1）、转化生长因子-β1（TGF-β1）、实时定量聚合酶链反应检测尿激酶型纤溶酶原激活物（uPA）和基质金属蛋白酶-2（MMP-2）。结果丹参素可明显抑制200 μmol/L乙醛诱导的HSCs增殖，MTT法和流式细胞仪检测结果显示，与对照组相比，丹参素可明显增加HSCs S期细胞的比例（P<0.05）。丹参素可下调HSC-T6细胞TGF-β1和派-1的mRNA表达，上调uPA的转录水平（P<0.01），而对MMP-2的转录水平无明显影响。结论丹参素能抑制HSC-T6的增殖和活化，并能调节细胞外基质积聚中的细胞因子，为肝纤维化的治疗提供了一种新的途径。
OBJECTIVE 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 (PAI-1), transforming growth factor-β1 (TGF-β1), 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 μmol/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 PAI-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.