【摘要】 目的考察氟维司群对垂体腺瘤GH3细胞凋亡的诱导作用和对小鼠的急性毒性作用。方法利用MTS法检测不同浓度氟维司群处理垂体腺瘤GH3细胞72 h后细胞的增殖活力,并计算半数抑制浓度(IC₅₀值)。氟维司群处理垂体腺瘤GH3细胞72 h后经Annexin V-FITC/PI双染,流式细胞仪检测细胞的凋亡率。采用最大限量法对小鼠进行氟维司群灌胃给药,每日观察小鼠行为情况,测定小鼠体重,记录死亡数,并计算半数致死量(LD₅₀)。14 d观察期结束采集小鼠实质性脏器制作石蜡组织切片进行病理学检查。结果氟维司群对垂体腺瘤GH3细胞作用72 h的IC₅₀为361.9 nM。流式细胞仪检测显示,氟维司群可剂量依赖性的诱导GH3细胞凋亡。急性毒性试验小鼠灌胃给药14 d后无中毒症状和死亡现象,即氟维司群对小鼠的半数致死量(LD₅₀)大于2 000 mg·kg^-1。石蜡组织切片观察发现与溶剂对照组相比,氟维司群组小鼠主要脏器均无任何肉眼可见的特征性病理变化。结论氟维司群具有一定诱导细胞凋亡的作用。但小鼠灌胃给药急性毒性较小,LD₅₀大于2 000 mg·kg^-1,安全性较好。更多还原

【Abstract】 Objective To investigate the effects of fulvestrant inducing apoptosis of pituitary adenoma GH3 cells and the acute toxicity of fulvestrant on mice. Methods After treated with fulvestrant for 72 h, the proliferative activity of pituitary adenoma GH3 cells was determined by MTS assay and 50% inhibitory concentration(IC₅₀). Simultaneously,the apoptosis ratios of pituitary adenoma GH3 induced by fulvestrant were detected by Annexin V-FITC/PI. The acute oral toxicity of fulvestrant in mice was used by the maximum limit method. The mice were observed daily to record the number of death and body weight, then 50% lethal dose(LD₅₀) was counted. Pathological examination was competed at the end of the 14 d observation period. Results The IC₅₀ of fulvestrant on pituitary adenoma GH3 cells was 361.9 n M. Fulvestrant could induce apoptosis of GH3 cells dose-dependently. There were no death mice in the 14 d acute oral toxicity test which means the LD₅₀ was greater than 2 000 mg·kg^-1. The fetal tissue of mice was found that there was no significant difference between the blank group and the fulvestrant treatment group according to the histopathology observation. Conclusion Fulvestrant induces apoptosis of pituitary adenoma GH3 cells. The acute toxicity of fulvestrant is low and the LD₅₀ was greater than 2 000 mg·kg^-1 which indicates that fulvestrant is safe.更多还原