目的 探討齊墩果酸對(duì)人肝癌HepG2細(xì)胞增殖的抑制作用和誘導(dǎo)凋亡作用，并考察其作用機(jī)制。方法 采用MTT法檢測(cè)齊墩果酸對(duì)HepG2細(xì)胞增殖的影響，吖啶橙/溴化乙錠（AO/EB）雙重染色法進(jìn)行細(xì)胞形態(tài)學(xué)觀察，流式細(xì)胞儀檢測(cè)細(xì)胞凋亡、活性氧（ROS）水平和線粒體膜電位（MMP）的變化。結(jié)果 隨著齊墩果酸濃度的升高，抑制率顯著增加，呈現(xiàn)明顯的時(shí)間與劑量相關(guān)性；齊墩果酸在25.0、50.0、100.0 μmol/L作用12 h時(shí)，細(xì)胞形態(tài)學(xué)發(fā)生改變，細(xì)胞的總凋亡率隨著齊墩果酸濃度的增加而升高，細(xì)胞中ROS水平隨著齊墩果酸濃度的增加而升高，細(xì)胞內(nèi)的MMP水平隨著齊墩果酸濃度的增加而降低。結(jié)論 齊墩果酸通過調(diào)節(jié)ROS和MMP體外抑制人肝癌HepG2細(xì)胞的增殖和誘導(dǎo)其凋亡

Objective To investigate the effect of oleanolic acid on proliferative inhibition and apoptotic induction against HepG2 cells, and explore its mechanism. Methods The cell inhibitory rates of oleanolic acid on HepG2 cells were assessed by MTT assay. The morphology of HepG2 cells was observed by acridine orange/ethidium bromide (AO/EB) double staining. The rate of apoptosis, change of reactive oxidative species (ROS) level, and mitochondrial membrane potential (MMP) were measured by flow cytometer method. Results The proliferation of HepG2 cells was inhibited by oleanolic acid with higher concentrations in a dose and time dependent manner. After be treated with oleanolic acid (25, 50, and 100 μmol/L) for 12 h, the morphology changes of cell apoptosis significantly observed, total apoptotic rates of HepG2 cells were increased, and level of ROS were obviously increased, while MMP were decreased. Conclusion Oleanolic acid can inhibit the proliferation and induce apoptosis in HepG2 in vitro, which is related to change of ROS and MMP.

國(guó)家自然科學(xué)基金資助項(xiàng)目（81101687）