Effect of caffeic acid phenethyl ester on proliferation and apoptosis of hepatic stellate cells in vitro.

Effect of caffeic acid phenethyl ester on proliferation and apoptosis of hepatic stellate cells in vitro.
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DOI:
10.3748/wjg.v9.i6.1278
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发表时间:
2003-06
影响因子:
4.3
通讯作者:
Wen-xing Zhao;Jing Zhao-;C. Liang;B. Zhao;R. Pang;Xing-Hua Pan
Wen-xing Zhao;Jing Zhao-;C. Liang;B. Zhao;R. Pang;Xing-Hua Pan
中科院分区:
医学2区
文献类型:
--
作者:
Wen-xing Zhao;Jing Zhao-;C. Liang;B. Zhao;R. Pang;Xing-Hua Pan

文献摘要

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目的探讨核因子-κ B(NF-κ B)抑制剂咖啡酸苯乙酯(CAPE)对大鼠肝星状细胞(HSC)增殖、胶原合成及凋亡的影响。方法分离培养大鼠HSCs,用CAPE处理。(3)H-胸腺嘧啶核苷(H-TdR)掺入法和H-脯氨酸(H-proline)掺入法检测HSCs增殖和胶原合成,原位杂交检测Ⅰ、Ⅲ型前胶原基因的表达。采用末端脱氧核苷酸转移酶介导的DIG-dUTP缺口末端标记法(TUNEL)检测凋亡细胞指数(AI)。结果CAPE在5 μ mol/L和10 μ mol/L浓度下分别显著抑制活化HSC的(3)H-TdR和(3)H-脯氨酸掺入。CAPE在高浓度时也能降低Ⅰ型前胶原基因表达(P<0.05)。CAPE可诱导HSC凋亡,凋亡指数呈时间和剂量依赖性增加,12 h从2.82 ± 0.73%增加到7.66 ± 1.25%(P<0.01),24 h从3.15 ± 0.88%增加到10.61 ± 2.88%(P<0.01)。结论低浓度CAPE抑制HSC增殖和胶原合成,高浓度CAPE诱导HSC凋亡。
AIM To investigate the role of nuclear factor-kappaB (NF-kappaB) inhibitor caffeic acid phenethy1 ester (CAPE) in the proliferation, collagen synthesis and apoptosis of hepatic stellate cells (HSCs) of rats. METHODS The HSCs from rats were isolated and cultured in Dulbecco's Modified Eagle's Medium (DMEM) and treated with CAPE. The proliferation and collagen synthesis of HSCs were determined by (3)H-TdR and (3)H-proline incorporation respectively, and the expression of type I, III procollagen genes was further explored by in situ hybridization. Apoptosis cell indices (AIs) were examined using terminal deoxynucleotidyl transferase- mediated DIG-dUTP nick end labeling (TUNEL). RESULTS In activated HSC in culture, CAPE significantly inhibited (3)H-TdR and (3)H-proline incorporation by HSCs at concentrations of 5 micromol/L and 10 micromol/L respectively. CAPE also reduced the type I procollagen gene expression (P<0.05) at higher concentration. Apoptosis of HSC was induced by CAPE and the AIs were time-and dose-dependently increased from 2.82+/-0.73 % to 7.66+/-1.25 % at 12 h (P<0.01) and from 3.15+/-0.88 % to 10.61+/-2.88 % at 24 h (P<0.01). CONCLUSION CAPE inhibits proliferation and collagen synthesis of HSC at lower concentration and induces HSC apoptosis at higher concentration.