本文選題：替芬泰　切入點(diǎn)：線粒體毒性　出處：《中國(guó)藥理學(xué)通報(bào)》2017年09期

【摘要】：目的采用HepG2細(xì)胞來評(píng)價(jià)首次合成的馬蹄金素衍生物替芬泰在抗乙肝病毒的同時(shí)對(duì)肝細(xì)胞的線粒體毒性,為臨床試驗(yàn)劑量設(shè)計(jì)和合理用藥提供參考。方法測(cè)定替芬泰對(duì)HepG2細(xì)胞增殖的抑制率,對(duì)培養(yǎng)上清液乳酸含量、細(xì)胞活性氧含量、線粒體膜電位變化及線粒體呼吸鏈復(fù)合物酶Ⅰ~Ⅳ活性的影響,綜合評(píng)價(jià)替芬泰的線粒體毒性。結(jié)果替芬泰對(duì)HepG2細(xì)胞增殖的半數(shù)抑制濃度為359μmol·L~(-1)。與對(duì)照組比較,替芬泰400μmol·L~(-1)(196 mg·L~(-1))時(shí)明顯降低HepG2細(xì)胞的線粒體膜電位,明顯增加細(xì)胞活性氧含量,升高乳酸生成水平,降低線粒體呼吸鏈復(fù)合物酶Ⅰ、Ⅱ、Ⅲ的活性,具有明顯的線粒體毒性。與拉米夫定、阿德福韋酯比較,同為100μmol·L~(-1)的替芬泰對(duì)上述指標(biāo)均無影響。結(jié)論替芬泰的線粒體毒性安全范圍較大,實(shí)驗(yàn)結(jié)果對(duì)臨床試驗(yàn)劑量設(shè)計(jì)和臨床用藥具有一定的指導(dǎo)意義。
[Abstract]:Objective to evaluate the mitochondrial toxicity of tefendai, the first synthetic chrysopanthin derivative, against hepatitis B virus (HBV) in hepatocytes by using HepG2 cells. Methods the inhibition rate of tifentai on HepG2 cell proliferation, the content of lactic acid in culture supernatant and the content of reactive oxygen species in cells were determined. The changes of mitochondrial membrane potential and the activity of mitochondrial respiratory chain complex enzyme 鈪，

本文編號(hào)：1681856