杂色曲霉素对小鼠肝脏细胞凋亡和增殖影响的研究

Effects of Sterigmatocystin on Apoptosis and Proliferation of Hepatocytes in KM Mice

目的 探讨杂色曲霉素 (ST)对小鼠肝细胞凋亡和增殖的影响。方法 采用动物实验和流式细胞光度方法定量检测灌喂不同剂量的ST和ST作用不同时间对小鼠肝细胞凋亡和增殖的影响。结果 经口灌喂不同剂量的ST(3μg kg ,30 μg kg,30 0 μg kg ,30 0 0 μg kg) 12h ,ST处理小鼠肝细胞的凋亡率均明显高于对照组 (P <0 0 1)。在 3～ 30 0 μg kg剂量范围内 ,ST剂量与凋亡率之间存在明显的量效正相关 (r=0 6 42 ,P <0 0 1)。同时 ,灌喂剂量为30 0 0 μg kg的ST后 6～ 48h ,随ST处理后时间的延长 ,肝细胞凋亡的增长率也明显增高 (r =0 72 2 ,P <0 0 1)。另外 ,ST尚有一定抑制肝细胞增殖的作用 ,但量效关系不明显 ,相同剂量ST(30 0 0 μg kg)处理小鼠后不同时间 (6～ 48h)与其对肝细胞增殖指数抑制率之间存在正相关 (r=0 46 9,P =0 0 2 1)。结论 经口给予ST可诱导。

Objective To explore the possible effects of sterigmatocystin(ST) on apoptosis and proliferation of hepatocytes in vivo.Methods In KM mice quantitative study was used with flow cytometric (FCM) method after oral administriation of ST at different dosages and different time.Results FCM analysis revealed that 12 hours after oral administration of ST at 4 different dosages (ST3μg/kg,30μg/kg,300μg/kg and 3 000μg/kg), the apoptosis rates of hepatocytes in all the ST treatment groups were significantly higher than that in control group (P<0.01). A dose-effect correlation could be found between ST dosages and apoptosis rates of hepatocytes within the dosage range from 3 to 300μg/kg(r=0.642, P<0.01). Six to fourty-eight hours after oral administration of ST at 3000μg/kg, significant positive correlation was found between the time periods after ST treatment and apoptosis rates increased with time on (r=0.722,P<0.01). Inhibiting effects of ST on the proliferation of hepatocytes could be found at some ST dosages, with no dose-effect correlation. Inhibiting rates of proliferation index of hepatocytes increased as the time prolonged after ST treatment (r=0.469,P=0.021). Conclusion Oral ST exposure could induce apoptosis of hepatocytes and inhibit proliferation of hepatocytes to some extent in mice.