酒精性肝纤维化及肝癌大鼠P53基因及ASPP蛋白的表达  

P53 Gene and ASPP Protein Family Expression in Liver of Rats with Alcoholic Hepatic Fibrosis and Hepatocirrhosis with Hepatoma

作　　者：刘俊玲[1] 何常[1,2] 孙江玲[1] 程明亮[3] 

机构地区：[1]贵阳医学院病理学教研室,贵州贵阳550004 [2]贵阳医学院附院病理科,贵州贵阳550004 [3]贵阳医学院附院感染科,贵州贵阳550004

出　　处：《贵阳医学院学报》2013年第6期582-587,共6页Journal of Guiyang Medical College

基　　金：国家科技部973计划经费资助(NO.2011CB512100);贵州省科技计划课题(黔科合SZ[2011]3001)

摘　　要：目的:研究不同白酒引起的酒精性肝纤维化、肝硬化合并肝癌大鼠肝组织中P53基因突变及其相关ASPP蛋白家族的表达。方法:运用A、B(分为低剂量D和高剂量G)2种白酒和黄曲霉素B1(AFB1)对大鼠进行处理,制备酒精性肝纤维化、肝硬化合并肝癌大鼠模型,用PCR及DNA测序技术检测大鼠肝脏组织中P53基因第5、6、7、8外显子的突变情况;用免疫组织化学Envision法检测大鼠肝脏组织中P53、P53凋亡刺激蛋白1(ASPP1)、ASPP2、ASPP家族抑制因子(iASPP)的表达。结果:成功制备了酒精性肝纤维化、肝硬化合并肝癌大鼠模型,不同白酒诱导大鼠肝纤维化、肝硬化合并肝癌的程度不同。免疫组化检测结果发现,P53及iASPP表达的阳性率在白酒B组(BD组和BG组)明显高于白酒A组(AD组和AG组),差异有统计学意义(P<0.05);ASPP1、ASPP2的阳性率在白酒B组(BD组和BG组)明显低于白酒A组(AD组和AG组),差异有统计学意义(P<0.05);iASPP表达量高的酒精性肝病和肝癌中,ASPP1、ASPP2表达量降低,差异有统计学意义(P<0.05);P53基因的突变检测显示P53的突变方式以碱基插入为主,其次为碱基突变及缺失;AD组和AG组突变率为42.3%,BD组和BG组突变率为78.3%,差异具有统计学意义(P<0.05)。结论:不同白酒对大鼠肝脏肝纤维化、肝硬化和肝硬化并肝癌的诱发程度不一样,可能与其对P53基因突变及P53相关蛋白(ASPP1、ASPP2、iASPP)表达影响不同有关。Objective： To explore of the expression of P53 gene and ASPP protein family in liver tis- sue of rats with hepatic fibrosis, hepatocirrbosis and hepatocirrhosis with hepatoma . Methods： The hepatic fibrosis, hepatocirrhosis combined with hepatoma rat model was established by using aflatoxin B1 （ AFB1 ） and 2 kind of liquor （ liquor A and B with low and high content） respectirely. Using immu- nohistochemistry to detect rat liver tissue P53, ASPP1, ASPP2, iASPP expression. Application of PCR technology to test rat liver tissue P53 gene exon 5, 6, 7, 8 expression. Results： The positive reaction rates of P53 and iASPP in group B were higher than those of group A, difference had statistical signifi- cance （ P 〈 0.05）. The positive reaction rates of ASPP1 and ASPP2 in group B were lower than those of group A, difference had statistical significance （P 〈 0.05 ）. In hepatic fibrosis, hepatocirrhosis and hepatocirrhosis with hepatoma, iASPP highly expressed, and ASPP1, ASPP2 lowly expressed, differ- ence had statistical significance（P 〈0.05）. P53 gene mutation detection showed that the main muta- tion way of P53 gene exon 5,6,7,8 was bases insert, followed by bases mutations and missing, group A mutation rate was 42.3%, group B mutation rate was 78.3%, difference had statistical significance （ P 〈 0.05 ）. Conclusions： Different liqueur has diverse inducing effects on hepatic fibrosis, hepatocir- rhosis and hepatocirrhosis with hepatoma, which may relate to their different influence on P53 gene mutation and P53 associated protein expression.

关 键 词：肝 纤维化 肝硬化 肝癌 基因 P53 P53凋亡刺激蛋白 基因突变 白酒 

分 类 号：K34-33[历史地理—历史学] K361.2[历史地理—世界史]