常规超声联合血清甲胎蛋白评估改良二乙基亚硝胺给药法诱导大鼠肝细胞肝癌模型的可行性  

Feasibility of conventional ultrasound combined with serum alpha-fetoprotein in the evaluation of modified diethylnitrosamine administration induced hepatocellular liver cancer model in rats

作　　者：苏天琳 王中会 晁旭[3] 樊莹莹[4] 黄峰[3] 杨兵社 SU Tianlin;WANG Zhonghui;CHAO Xu;FAN Yingying;HUANG Feng;YANG Bingshe(Faculty of Medical Technology,Shaanxi University of Chinese Medicine,Xi′an 712046,Shaanxi Province,China;School of Basic Medical Sciences,Shaanxi University of Chinese Medicine,Xi′an 712046,Shaanxi Province,China;Scientific Research,the Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi Province,China;Department of Ultrasound,the Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi Province,China)

机构地区：[1]陕西中医药大学医学技术学院,陕西西安712046 [2]陕西中医药大学基础医学院,陕西西安712046 [3]陕西中医药大学第二附属医院科研科,陕西咸阳712000 [4]陕西中医药大学第二附属医院超声科,陕西咸阳712000

出　　处：《新乡医学院学报》2022年第8期708-714,共7页Journal of Xinxiang Medical University

基　　金：陕西省科技计划项目(编号:2020SF-324);陕西省中医药管理局科技计划项目(编号:2017LCPT037);陕西中医药大学消化病肿瘤分子机制及中西医结合防治基础研究创新团队项目(编号:2019-YS05);陕西中医药大学第二附属医院学科创新团队项目(编号:2020 XKTD-B05)。

摘　　要：目的探讨改良二乙基亚硝胺(DEN)给药法诱导大鼠肝细胞肝癌(HCC)模型及常规超声联合血清甲胎蛋白(AFP)评估HCC模型的可行性。方法将175只无特定病原体级雄性Sprague-Dawley大鼠随机分为空白对照组(n=8)、对照组(n=69)和模型组(n=98)。对照组大鼠给予单一剂量DEN(50 mg·kg^(-1))腹腔注射制备HCC模型。模型组大鼠采用改良DEN给药法诱导大鼠HCC,即根据体质量变化动态调整DEN给药剂量:初始剂量50 mg·kg^(-1),然后每周根据体质量变化调整给药剂量,若大鼠体质量未下降或下降幅度小于每周5 g时,按50 mg·kg^(-1)给药;若每周大鼠体质量下降5~20 g,按25 mg·kg^(-1)给药;若大鼠体质量下降超过每周20 g,暂停给药1周。空白对照组大鼠腹腔注射等量的生理盐水。第1~4周每周给药2次,第5~15周每周给药1次,连续给药15周。造模完成后,记录并比较造模期间3组大鼠死亡率;对存活大鼠行肝脏超声、血清AFP水平检查。随机抽取空白对照组7只大鼠、对照组14只大鼠和模型组14只大鼠,麻醉后处死并解剖,观察肝脏成瘤情况,记录肝脏质量并计算肝脏指数,苏木精-伊红染色观察大鼠肝脏病理学变化。结果造模期间,空白对照组、对照组、模型组大鼠死亡率分别为0.0%(0/8)、34.8%(24/69)、19.4%(19/98);对照组大鼠死亡率显著高于空白对照组(χ^(2)=4.043,P<0.05),模型组与空白对照组大鼠死亡率比较差异无统计学意义(χ^(2)=1.890,P>0.05),模型组大鼠死亡率显著低于对照组(χ^(2)=5.019,P<0.05)。空白对照组大鼠均未见癌结节或肝硬化表现,超声影像正常。对照组30只、模型组48只大鼠肝脏可见癌结节,癌结节超声检出率分别为66.7%(30/45)、60.8%(48/79);对照组与模型组大鼠的肝脏癌结节超声检出率比较差异无统计学意义(χ^(2)=0.278,P>0.05)。对照组与模型组大鼠血清AFP水平显著高于空白对照组(t=0.728、0.771,P<0.05);对照组与模型组大鼠血�Objective To investigate the feasibility of modified diethylnitrosamine(DEN)administration induced hepatocellular liver cancer(HCC)in rats and conventional ultrasound combined with serum alpha-fetoprotein(AFP)in the evaluation of HCC model.Methods One hundred and seventy-five specific pathogen free male Sprague-Dawley rats were randomly divided into blank control group(n=8),control group(n=69)and model group(n=98).The rats in the control group were given a single dose of DEN(50 mg·kg^(-1))intraperitoneally to prepare HCC model.The rats in the model group were treated with modified DEN administration to induce HCC,the dose of DEN was adjusted dynamically according to the change of body mass:the initial dose was 50 mg·kg^(-1),and then the dose was adjusted weekly according to the change of body mass,if the body weight of rats did not decrease or the decrease was less than 5 g in one week,the drug was administered at the dose of 50 mg·kg^(-1);if the body mass of rats decreased in the range of 5-20 g in one week,the drug was administered at 25 mg·kg^(-1);if the body mass of rats decreased and the rate of decrease of body mass of rats exceeded 20 g in one week,the drug was suspended for one week.Rats in the blank control group were injected intraperitoneally with an equal amount of saline.The rats were administered twice a week from the 1^(st) to the 4^(th) week,and once a week from the 5^(th) to the 15^(th) week,and continuously for 15 weeks.After the completion of modeling,the mortality rate of the rats in the three groups during the modeling period was recorded and compared;liver ultrasound and serum AFP levels were examined in the surviving rats.Seven rats in the blank control group,14 rats in the control group and 14 rats in the model group were randomly selected,they were anesthetized and executed,and the liver tumor formation of the rats were observed,the liver weight of the rats was recorded and the liver index was calculated,and the pathological changes of liver of the rats were observed by hematoxylin-eo

关 键 词：肝细胞肝癌 二乙基亚硝胺 超声成像 甲胎蛋白 

分 类 号：R735.7[医药卫生—肿瘤]