目的构建小鼠早期肺腺癌模型,为影像学研究提供工具。方法 210只KM小鼠随机分为5个实验组(每组各40只)和1个对照组(10只)。实验组每周皮下注射亚硝基胍(MNNG)溶液0.2 m L(浓度2.0 mg/m L),按总剂量分为A、B、C、D和E组,分别注射1、2、4、8和12周。于首次注射后的第60、80、100、120天在每组中随机抽取10只处死,解剖肺脏并观察肿瘤鼠发生率、肿瘤数量和大小等。对照组每周皮下注射0.2 m L的生理盐水共12周。结果 1成瘤率和成瘤总数与时间、剂量呈正相关,但首次注射第60天时,实验组均无肿瘤生成。2第80天时,A、B、C、D、E组的成瘤率分别为0%、10%、30%、40%和50%,成瘤总数分别为0、4、42、60和81个,直径<0.5 mm的肿瘤数分别为0、4、25、31和40个。3第100天时,每组的成瘤率分别为20%、40%、100%、100%和100%,成瘤总数分别为6、19、187、223和301个,直径<0.5 mm的肿瘤数分别为5、16、132、124和123个。4第120天时,每组的成瘤率分别为30%、50%、100%、100%、100%,成瘤总数分别为30、124、302、351和362个,直径<0.5 mm的肿瘤数分别为21、98、123、140和108个。经病理证实这些肺肿瘤均为肺腺癌。结论浓度为2.0 mg/m L的亚硝基胍溶液0.2 m L每周皮下注射,连续四周,100 d时能获得100%的肺腺癌成瘤率和最多的<0.5 mm肿瘤数,为最佳的小鼠早期肺腺癌模型。
Objective To establish a mouse model of early lung adenocarcinoma to serve the imaging studies of early lung adenocarcinoma .Methods Two-hundred and ten 4-week old SPF female Kunming mice were randomly divided into 5 experimental groups (40 mice per group) and 1 control group (10 mice).The mice of experimental groups were subcutaneously injected with a dose of 0.2 ml 1-methyl-3-nitro-1-nitroso-guanidine ( MNNG) solution in concentration of 2.0 mg/mL weekly for 1, 2, 4, 8, 12 weeks (group A-E), respectively, while the mice of control group was subcutane-ously injected with 0.2 mL saline weekly for 12 weeks.Ten mice were randomly sacrificed from each experimental group at the 60th, 80th, 100th and 120th days after initial injection ( group A60 , group A80 , group A100 , group A120; group B60 ,……and so on) , and the bilateral lungs were dissected .The tumor occurrence rate , number and size of lung tumors were observedandrecorded.Results 1.Thetumoroccurrencerateandnumberoflungtumorswerepositivelyproportionalto the time and dose of MNNG injection .No tumor was found in any group at the 60th day.2.At the 80th day, the tumor oc-currence rate in the groups A, B, C, D and E was 0, 10%, 30%, 40%and 50%, respectively.The number of tumors in each group was 0, 4, 42, 60 and 81, respectively.The number of tumors smaller than 0.5 mm in diameter was 0, 4, 25, 31 and 40, respectively.3.At the 100th day, the tumor occurrence rate was 20%, 40%, 100%, 100%and 100%, re-spectively.The number of tumors was 6, 19, 187, 223 and 301, respectively, and the number of tumors smaller than 0.5 mm in diameter was 5, 16, 132, 124 and 123, respectively.4.At the 120th day, the tumor occurrence rate was 30%, 50%, 100%, 100%and 100%, respectively.The number of tumors was 30, 124, 302, 351 and 362 per group, respec-tively.The number of tumors smaller than 0.5 mm in diameter was 21, 98, 123, 140 and 108, respectively.The induced lung adenocarcinomas were confirmed by pathology .Conclusions MNNG solution 0.2 mL (2.0 mg/mL) subcutaneously inje