氧化应激反应在二乙基亚硝胺诱导大鼠肝癌形成过程中的动态变化及意义  

Dynamic changes and significance of oxidative stress in the formation of rat liver cancer induced by diethylnitrosamine

作　　者：钟长军 王秀[2] 罗佳佳 ZHONG Changjun;WANG Xiu;LUO Jiajia(Anhui College of Traditional Chinese Medicine, Wuhu 241003, Anhui, China;Research Center of Integrated Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu 241002, Anhui, China)

机构地区：[1]安徽中医药高等专科学校,安徽芜湖241003 [2]皖南医学院中西医结合研究中心,安徽芜湖241002

出　　处：《现代中西医结合杂志》2021年第12期1261-1265,1270,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：皖南医学院重点科研项目培育基金(WK2014Z09)。

摘　　要：目的探讨氧化应激反应在二乙基亚硝胺诱导大鼠肝癌过程中的动态变化及意义。方法雄性SD大鼠36只,随机分为模型组24只和正常组12只。模型组大鼠予以50 mg/kg二乙基亚硝胺腹腔注射,前4周每周2次,后每周1次,持续注射16周;正常组大鼠同模型组方法予以生理盐水腹腔注射。分别于实验第4,8,12,16周末取材,观察2组大鼠体重、肝脏系数、肝脏病理、肝组织中活性氧(ROS)及血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ谷氨酰转肽酶(γ-GT)、丙二醛(MDA)、8-羟基脱氧鸟苷(8-OHdG)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)的动态变化。结果模型组大鼠实验第4,8,12,16周的体重均明显低于同期正常组(P均<0.05),肝脏系数均明显高于同期正常组(P均<0.05)。肝脏病理检测发现模型组大鼠存在明显的组织损伤、炎性反应-肝纤维化-肝癌的动态变化过程。模型组大鼠实验第4,8,12,16周的肝组织中ROS及血清ALT、AST、γ-GT、MDA、8-OHdG水平均显著高于同期正常组(P均<0.05),并且随着时间的延长均显著增高(P均<0.05);血清GSH-Px、SOD水平均显著低于同期正常组(P均<0.05),但是随着时间的延长降低不明显(P均>0.05)。结论在二乙基亚硝胺诱导大鼠肝癌的过程中存在严重的氧化应激,并随着诱导时间延长存在明显加重趋势,这种持续的氧化应激状态可能是导致肝癌发生、发展的重要原因。Objective It is to investigate the dynamic changes and significance of oxidative stress in the process of diethylnitrosamine-induced liver cancer in rats.Methods Thirty-six male SD rats were randomly divided into a model group(n=24)and a normal group(n=12).The rats in the model group were injected intraperitoneally with 50 mg/kg diethylnitrosamine,twice a week for the first 4 weeks and once a week after that for 16 weeks;the rats in the normal group were injected intraperitoneally with normal saline in the same way as the model group.The materials were collected on the 4th,8th,12th,and 16th weekend of the experiment to observe the dynamic changes of body weight,liver coefficient,liver pathology,reactive oxygen species(ROS)in the liver tissue,the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma glutamyl transpeptidase(γ-GT),malondialdehyde(MDA),8-hydroxydeoxyguanosine(8-OHdG),glutathione peroxidase(GSH-Px),superoxide dismutation(SOD)in the rats of the two groups.Results The body weight of rats in the model group was significantly lower than that of the normal group at the same period at 4,8,12,and 16 weeks(P<0.05),and the liver coefficient was significantly higher than that of the normal group at the same period(P<0.05).Liver pathological examination showed that the model group rats had obvious tissue damage,and dynamic change process of inflammatory reaction-liver fibrosis-liver cancer.The levels of ROS in liver tissue and ALT,AST,γ-GT,MDA and 8-OHdG in serum of rats in the model group at the 4th,8th,12th,and 16th week of the experiment were significantly higher than those in the normal group during the same period(all P<0.05),and they all increased significantly with time(all P<0.05);the levels of serum GSH-Px and SOD in serum were significantly lower than those of the normal group during the same period(all P<0.05),but the decrease was not obvious with the extension of time(all P>0.05).Conclusion There is severe oxidative stress in the process of diethylnitrosamine inducing

关 键 词：二乙基亚硝胺 氧化应激 肝癌 

分 类 号：R-332[医药卫生]