中文摘要：

目的探讨皮秒脉冲电场（picosecond pulse electric field,ps PEF）治疗裸鼠宫颈癌动物模型的体内效应及机制。方法将36只裸鼠宫颈癌动物模型编号后随机抽取24只分为对照组、脉冲治疗后6 h组、脉冲治疗后12 h组、脉冲治疗后24 h组,每组6只。治疗组给予固定脉冲参数（脉冲个数2 000个,脉宽800 ps,电压70 k V,频率3 Hz）的脉冲电场处理,对照组不予脉冲电场处理。取肿瘤组织,采用HE染色、透射电镜观察肿瘤组织形态学变化。TUNEL试剂盒检测肿瘤组织凋亡程度。JC-1染色激光共聚焦显微镜下检测肿瘤组织线粒体跨膜电位。应用蛋白活性测定试剂盒检测Caspase-3、Caspase-8、Caspase-9、Caspase-12蛋白活性。其余12只动物模型随机抽取分为治疗组和对照组,脉冲电场处理后每隔3 d测量肿瘤体积,计算相对肿瘤增殖率T/C（%）。结果治疗后肿瘤组织发生不同程度的坏死,以治疗后24 h最重,电镜下可见凋亡小体,以治疗后12 h组多见。各治疗组肿瘤组织凋亡率均高于对照组（P〈0.01）,12 h组凋亡率明显高于其余两个治疗组和对照组（P〈0.01）。脉冲治疗后随时间的延长线粒体膜电位逐渐降低。Caspase-3、Caspase-12蛋白活性检测结果均显示12 h组明显高于其他治疗组和对照组（P〈0.01）。Caspase-8、Caspase-9蛋白活性各组之间无明显差异。治疗后3、6、9 d两组肿瘤体积有统计学差异,处理组相对肿瘤增殖率分别为76.87%、71%、68.87%。结论 ps PEF可以作用于宫颈癌动物模型的肿瘤部位,导致肿瘤组织发生坏死及凋亡,早期对肿瘤的生长有一定的抑制作用。

英文摘要：

Objective To determine the damaging effect of picosecond pulse electric field（ ps PEF）on the nude mice model of cervical cancer and investigate the underlying possible mechanism. Methods Nude rat xenograft model of cervical cancer was established by implanting He La cells in the back of the animals. Among the 36 rats with tumor mass over 1 cm in size,24 were randomly chosen and then divided into control group,and groups in 6,12 and 24 h after treatment. Treatment group were treated under a ps PEF of pulse number 2 000,pulse width 800 ps,voltage 70 k V,and frequency 3 Hz,and control group received no such treatment. After the tumor mass were harvested at the corresponding time points,tumor morphology was observed by using HE staining and transmission electron microscopy（ TEM）,cell apoptosis was determined by TUNEL. Mitochondrial transmembrane potential was assessed by Jc-1 staining on laser scanning confocal microscopy（ LSCM）. The activity of caspase-3,8,9 and 12 were detected by activity assay kit. Another 12 animal model were randomly divided into the treatment group and control group,the tumor volume we measured every 3 days after ps PEF treatment and the relative tumor proliferation rate was calculated. Results Tumor tissue occurred necrosis at different degrees after treatment,and the tissue from 24 h after treatment was heaviest. Electron microscopy showed apoptotic bodies in the tumor cells,most commonly in the cells from 12 h after treatment. The apoptotic rate was significantly higher in all the treatment groups than the control group,and the 12 h group was significantly greater than the other groups（ P 〈 0. 01）. Mitochondrial membrane potential was decreased with the extension of treatment time. The activities of proteins caspase-3 and-12 was significantly higher in the 12 h group than the other groups,and those of caspase-8 and-9 had no significant difference among the treatment groups and control group. There were significant differences in tumor volume between the control group and t