敲低星形胶质细胞上调基因-1表达对二乙基亚硝胺诱导的大鼠原发性肝癌的调控作用  

Effect of Knocking down Astrocyte Elevated Gene-1 on Diethylnitro-samine-induced Primary Hepatocellular Carcinoma in Rats

作　　者：陈建雄 季茹 蔡庆 张茜 CHEN Jianxiong;JI Ru;CAI Qing;ZHANG Qian(Department of Hepatobiliary Surgery,General Hospital of Southern Theater Command,Guangzhou,510010,China)

机构地区：[1]南部战区总医院肝胆外科,广州市510010

出　　处：《医学分子生物学杂志》2024年第4期323-328,共6页Journal of Medical Molecular Biology

基　　金：广东省医学科技计划项目(No.B2023490)。

摘　　要：目的探讨敲低星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)表达对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的原发性肝癌的调控。方法将60只大鼠随机分成Control组、DEN组、AEG-1 NC KO DEN组及AEG-1 KO DEN组,每组15只。除Control组外,其余组均以DEN灌胃构建大鼠原发性肝癌模型,Control组和DEN组大鼠每日灌胃等体积生理盐水。AEG-1 KO DEN组和AEG-1 NC KO DEN组分别经腹腔注射稳定转染AEG-1shRNA或shRNA-NC慢病毒表达载体的HCCLM6。比较各组肝脏细胞损伤、凋亡、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷肽甘肽(glutathione peroxidase,GSH)、肝功能,血清IL-6、TNF-α含量,肝脏组织半胱氨酸蛋白酶3(caspase-3,Cas-3)、半胱氨酸蛋白酶9(caspase-9,Cas-9)表达及P65蛋白表达。结果DEN组AEG-1的表达水平明显高于Control组(P<0.05),AEG-1 KO DEN组的大鼠死亡率及腹水发生率低于DEN组(P<0.05);AEG-1 KO DEN组血清AST、ALT、IL-6和TNF-α水平低于DEN组(P<0.05),SOD活性高于DEN组(P<0.05),GSH和MDA含量低于DEN组(P<0.05),cleaved cas9/cas9、cleaved cas3/cas3和p-P65/P65蛋白表达低于DEN组(P<0.05)。结论AEG-1敲除可降低DEN诱导的大鼠的氧化应激水平以及炎症因子水平,减轻对肝脏组织的损伤,改善肝脏功能。Objective To explore the effect of knocking down astrocyte elevated gene-1(AEG-1)on diethylnitrosamine(DEN)-induced primary hepatocellular carcinoma(PHC).Methods A total of 60 rats were randomly divided into 4 groups:Control group,DEN group,AEG-1 NC KO DEN group and AEG-1 KO DEN group,15 rats in each group.Rats were given intragastric administration of DEN to construct PHC models in each group except in the Control group,while rats in the Control group were given the same volume of normal saline.The rats in AEG-1 KO DEN group and AEG-1 NC KO DEN group were given intraperitoneal injection of HCCLM6 with stably transfected AEG-1 shRNA or shRNA-NC lentivirus expression vector,respectively.The liver cell damage,apoptosis,levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH),liver function,levels of serum IL-6 and TNF-α,expressions of caspase-3(Cas-3),caspase-9(Cas-9)and P65 in liver tissues were compared among each group.Results The expression level of AEG-1 in the DEN group was significantly higher than that in the Control group(P<0.05).The mortality of rats and incidence of ascites in the AEG-1 KO DEN group were lower than those in the DEN group(P<0.05),and the levels of serum AST,ALT,IL-6 and TNF-αwere lower than those in the DEN group(P<0.05),SOD activity was higher than that in the DEN group(P<0.05),levels of GSH and MDA were lower than those in the DEN group(P<0.05),and expressions levels of cleaved cas9/cas9,cleaved cas3/cas3 and p-P65/P65 were lower than those in the DEN group(P<0.05).Conclusion Knocking out AEG-1 can reduce the levels of oxidative stress and inflammatory factors induced by DEN,relieve liver tissue damage and improve liver function in rats.

关 键 词：星形胶质细胞上调基因-1 二乙基亚硝胺 原发性肝癌 

分 类 号：Q786[生物学—分子生物学]