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吴晨,连灵君,徐进,王秀敏,徐立红.铅对小鼠肝脏超微结构及凋亡相关蛋白p53、Bax、Bcl-2表达的影响[J].环境科学学报,2006,26(9):1510-1514

Effects of lead on the ultrastructure and expression of p53、Bax and Bcl-2 in mice liver

摘要：为探讨铅对小鼠肝脏超微结构及凋亡相关蛋白p53、Bax、Bcl-2表达的影响,取刚断奶的ICR雄性小鼠25只,随机分为5组,以10、50、100、500mg·kg^-1的醋酸铅隔天灌胃,连续28天,对照组灌高纯水.用westernblot法检测肝组织中p53、Bax及Bcl-2表达量,并用肝做病理组织切片.病理切片可见在高浓度组(100、500mg·kg^-1)肝细胞结构损伤比较严重、细胞核体积缩小、染色质浓缩、线粒体肿胀、基质变淡、不均匀、嵴消失,并出现空泡及线粒体的崩解;50mg·kg^-1组可看到内质网的增生和扩张.在最低浓度组(10mg·kg^-1),p53和Bax的表达量明显升高,与对照组相比差异有显著性(p<0.05);随着染毒浓度的升高,二者的表达量又逐渐下降,到最高浓度组(500mg·kg^-1)时,p53和Bax的表达量又明显低于对照组,差异有显著性(p<0.05).10、50、100mg·kg^-1Bcl-2表达量没有明显的变化,最高浓度组时明显低于对照组(p<0.05).结果显示,铅在高浓度时可严重损害肝细胞结构,在低浓度时可诱导小鼠肝组织中p53和bax基因表达上调,这可能与铅诱导细胞凋亡作用有关.

Abstract：To investigate the effects of lead acetate on the ultrastructure and the expression of p53、Bax and Bcl-2 in mice liver. Twenty five ICR mouse were randomly assigned into five groups and administrated by oral gavage with 0,10,50,100,500 mg·kg^-1 body weight of lead acetate every other day for successive 28 days. The expression of p53, Bax and Bcl-2 in liver were measured by western blotting. Meanwhile, the tissue slices of liver were made for ultrastructure observation. By electron microscopy, it can be observed that nuclear chromatin condensed, nuclear membrane shrank, mitochondria swelled and ruptured at the dosage of 100 and 500 mg·kg^-1 obviously. The expression of p53 was significantly higher than that of control (p<0.05) at the dosage of 10 mg·kg^-1 body weight as well as Bax. But as the increasing of dosage, they were decreased steadily and significantly lower than that of control (p<0.05) at the dosage of 500 mg·kg^-1 body weight. However, the expression of Bcl-2 showed no difference in lead-treated groups compared with control group except for the highest group. The results showed that the ultrastructure of hepatocytes were destoryed at the higher dosage, foremore, p53 and bax were up-regulated which may be associated with hepatocytes apoptosis.