土贝母苷甲诱导的人宫颈癌HeLa细胞凋亡的超微结构变化及环孢菌素A的保护作用

Tubeimoside I-induced ultrastructural changes of human cervical carcinoma HeLa cell line and the protective effect of cyclosporine A

目的观察土贝母苷甲(TBMS1)诱导的人宫颈癌HeLa细胞凋亡的超微结构变化及环孢菌素A的保护效果,探讨以线粒体为中心的内源性凋亡途径在TBMS1诱导人宫颈癌HeLa细胞凋亡时的作用。方法利用透射电镜观察不同浓度TBMS1作用不同时间引起的细胞超微结构的变化,以及环孢菌素A预处理对TBMS1作用的影响。结果随着土贝母TBMS1浓度的增高和作用时间的延长,人HeLa细胞的结构发生了连续性变化。肿瘤细胞逐渐减小,细胞间隙逐渐增大,线粒体逐渐肿胀、退化,粗面内质网逐渐扩张,核逐渐变小、核碎裂。在TBMS1低浓度时,环孢菌素A能够在一定程度上保护细胞免受TBMS1的损伤。环孢菌素A对TBMS1的损伤有保护效果。但当TBMS1浓度增大时,环孢菌素A的这种保护就不起作用了。结论TBMS1诱导HeLa细胞发生一系列凋亡特征的超微结构变化,线粒体肿胀、退化为其特征之一,从形态学角度提供了以线粒体为中心的内源性凋亡途径起一定作用。

Objective To observe the ultrastructural changes of HeLa cells in response to tubeimoside I （TBMS1） treatment and the protective effect of cyclosporine A （CsA）, and explore the role of intrinsic apoptosis pathway in TBMS l-induced HeLa cell apoptosis. Methods HeLa cells were treated with TBMS1 （10-50 μmo/L） alone or in combination with 2 μmol/L CsA for 12 and 24 h and observed with transmission electron microscope （TEM） for the ultrastructural changes of the cells. Results TBMSI induced apoptosis of HeLa cells in a concentration- and time-dependant manner. Under TEM, the treated cells progressively shrunk and the intercellular space widened with loss of microvillns, mitochondrial swelling, rough endoplasmicreticulumenlargement, chromatincondensation, nuclear shrinkage and nuclear pyknosis as TBMS l concentration increased. At low concentrations, CsA offered partial protection of the mitochondria from TBMSl-induced damage whereas high-concentration CsA did not. Conclusion TBMSI induces ultrastructural changes typical for apoptosis of the HeLa cells, which provides morphological evidence for the role of intrinsic apoptosis pathway in TBMSI-induced apoptosis.