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

机译:咖啡酸苯乙酯对肝星状细胞增殖和凋亡的影响

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AIM: To investigate the role of nuclear factor-κB (NF-κB) inhibitor caffeic acid phenethyl 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 ~3H-TdR and ~3H-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 ~3H-TdR and ~3H-proline incorporation by HSCs at concentrations of 5 μmol/L and 10 μmol/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.
机译:目的:探讨核因子-κB(NF-κB)抑制剂咖啡酸苯乙酯(CAPE)在大鼠肝星状细胞(HSCs)增殖,胶原合成和凋亡中的作用。方法:分离大鼠HSC,并在Dulbecco改良Eagle培养基(DMEM)中培养,并用CAPE处理。分别通过〜3H-TdR和〜3H-脯氨酸掺入确定HSCs的增殖和胶原合成,并通过原位杂交进一步探索Ⅰ,Ⅲ型胶原蛋白基因的表达。使用末端脱氧核苷酸转移酶介导的DIG-dUTP缺口末端标记(TUNEL)检查凋亡细胞指数(AIs)。结果:在活化的HSC培养物中,CAPE分别以5μmol/ L和10μmol/ L的浓度显着抑制HSCs〜3H-TdR和〜3H-脯氨酸的掺入。高浓度时CAPE还降低了Ⅰ型胶原蛋白的基因表达(P <0.05)。 CAPE诱导HSC凋亡,并且AIs随时间和剂量依赖性从12h时的2.82 + -0.73%增加到7.66 + -1.25%(P <0.01)和从3.15 + -0.88%增加到10.61 + -2.88在24小时的%(P <0.01)。结论:CAPE在较低浓度下抑制HSC的增殖和胶原合成,在较高浓度下诱导HSC凋亡。

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