树鼩肝癌形成过程中凋亡抑制基因的表达及与细胞凋亡的关系(英文)

Relationship between the expression of survivin and the cellular apoptosis during the development of tree shrew liver cancer

背景:目前对肝细胞癌(HCC)的研究大多数只局限于对人的肝癌及癌旁组织进行研究,这种研究方法的最大缺陷是不能动态观察肝癌形成过程中的不同时期的各种变化。目的:利用实验诱发树鼠句肝癌的动物模型,动态研究在树鼠句肝癌形成过程中凋亡抑制基因(survivin)的表达及其抑制凋亡的机制。设计:完全随机对照实验。干预:实验组给予AFB1(黄曲霉毒素B1)105周,然后继续喂正常饲料至150周。对照组动物不喂AFB1,仅按正常饲养方法同样喂至150周。实验期间每隔15周对实验组和对照组动物打开腹腔进行肝组织活检。活检组织用40g/L中性甲醛固定,石蜡包埋。然后将对照组30,60,90周和实验组30,60周及HCC组织的切片,采用免疫组织化学S-P法和脱氧核糖核酸末端转移酶介导的缺口末端标记(TUNEL)技术,进行sur-vivin基因蛋白和凋亡细胞的检测。主要观察指标:树鼠句肝细胞癌形成过程中每一阶段的survivin基因蛋白的表达情况和细胞凋亡的情况。结果:survivin基因与HCC的发生有关,在树鼠句HCC形成过程中,其表达呈递增趋势。survivin在对照组30,60,90周,实验组30,60周平均得分分别为0.62,0.77,0.92,1.02,1.6,在树鼠句HCC组织切片中平均得分为5.34,与各组肝组织中的表达差异有显著性意义(t=3.0580,3.2564,3.0316,4.7715,3.8036,P<0.

BACKGROUND:At pres en t,studies on hepatocellul ar carcinoma (HCC)are mostly confined to those on h uman HCC and the surrounding tissues.The biggest deficiency of these kinds of study methods is incapable of observ ing dynamically various changes of diff ere nt periods during the formation o f HCC.OBJECTIVE:To explore the expression of the apop tosis-inhibiting gene(survivin)and its mechanism of inhibiting apop tosis during the development of tree shrew liver cancer.DESIGN:The healthy w ildlife tree shrews were divided at randominto trial and the control groups.INT ERVENTION:For the trial group,animals were fed with AFB 1 (aflatoxin B 1 )till the 105th week,and then with normal animal food till the 150th week when experiment ended.For the contr ol group,animals were merely fed wit h normal animal food till the 150th wee k.During the experiment,biopsies o f the liver tissues were carried out at 30t h,60th,and 90th week in the two groups.The biopsy tissues were fixed in 40g /L formalehyde and embedded in paraf-fin.Whereafter,the tissue section s of the 30th,60th,and 90t h week from the control group and the 30th,60th week,and HCC from the tria l group,were stained with immunochemistry S-P me thod and terminal deoxynucleo tidyl transferase-mediated nick end labeling(TUNEL)technique,were for the su r-vivin gene expression and the apopto sis cells.MAIN OUTCOME MEASURE:The exp ression of survivin gene and t he apoptosis ofcells inevery stage dur ing the de velopmentoftree shrewliv er cancer.RESULTS:The occurrence of HCC had relation wi th gene survivin whose ex-pression was in an increasing trend.The mean scor es of surviving gene ex-pression in the control group at 30th,60th and 9 0th week and in the trial group at 30th and 60th week were 0.62,0.7 7,0.92,1.02and 1.6respectively.The mean score in the HCC tissue s ections was 5.34,which had significant differ-ence compared with that in e ach group(t=3.0580,3.2564,3.0316,4.7715,3.803 6,P<0.01).The surviving expression has a negative correlati on with the apoptotic index and an effect on proh ibiting the cellular apoptosis .