【摘要】 目的研究鬼臼毒素纳米脂质载体(POD-NLC)对永生化人宫颈上皮细胞(H8细胞)的凋亡诱导作用及机制。方法采用超声乳化法制备POD-NLC,分别以不同质量浓度(0.000 1、0.001、0.01、0.1、1μg/ml)的POD-NLC和鬼臼毒素(POD)处理H8细胞,采用MTT法检测细胞增殖抑制率,流式细胞术(FCM)检测细胞凋亡率,荧光显微镜和透射电镜观察细胞形态变化。结果 POD-NLC和POD干预后均能抑制H8细胞增殖,且呈时间和剂量依赖性,在同一时间相同浓度条件下,POD-NLC干预后细胞增殖抑制率明显高于POD干预后;0.01μg/ml的POD-NLC干预H8细胞24、48 h后细胞凋亡率均明显高于POD。POD-NLC和POD干预H8细胞48 h后,荧光显微镜和透射电镜下观察均出现核固缩、染色质高度凝聚、凋亡小体等典型的凋亡形态改变。结论与POD相比,POD-NLC对H8细胞具有更强的增殖抑制和凋亡诱导效果,其机制可能为POD经NLC包裹后对组织的黏附性增大,更易黏附于细胞表面,细胞内的药物浓度提高。更多还原

【Abstract】 Objective To investigate the apoptosis-inducing effect and its mechanism of podophyllotoxin nanostructured lipid carriers(POD-NLC) in immortalized human cervical epithelial cells(H8 cells).Methods POD-NLC was prepared by using microemulsion technique.H8 cells were respectively treated with POD-NLC or podophyllotoxin(POD) at different concentrations of 0.000 1,0.001,0.01,0.1,1 μg/ml.The proliferation of the cells was evaluated by using MTT assay,and apoptotic index was determined by using flow cytometry(FCM).Additionally,the changes of cell morphology were observed under fluorescence microscopy and electron microscopy.Results Both POD-NLC and POD inhibited the proliferation of H8 cells effectively,and showed time and dose-dependence,under the same conditions,the inhibitory effect of POD-NLC was significantly higher than that of POD;After treatment of POD-NLC or POD for 24 h or 48 h(both 0.01 μg/ml),the apoptosis rate of H8 cells stimulated by POD-NLC were significantly higher than that by POD.Forty-eight hours after the treatment of POD-NLC and POD,H8 cells appeared typical morphological changes of apoptosis under fluorescence microscopy and transmission electron microscopy.Conclusions POD-NLC has more prominent inhibitory and apoptosis-inducing effect on H8 cells,its possible mechanism is that POD wrapped by NLC can strengthen significantly adhesion of the organization and cell,and can increase remarkably intracellular drug concentration.更多还原