【摘要】 背景与目的目前常用的肺癌移植瘤模型和致癌剂诱发的大、小鼠肺肿瘤等动物模型均存在不同程度的缺陷,构建方法有待进一步完善。本研究拟建立一种简便可行的肺肿瘤动物模型构建方法,为肺肿瘤的发病机理研究以及筛选、评估肺肿瘤的防治方法提供一种有效的模型工具。方法购置36只体重180～220g雌性Sprague Dawley(SD)大鼠,适应性喂养1周,随机分为两组,每组18只。模型组给予0.2mL(只/次)3,4-苯并芘-玉米油(含3,4-苯并芘2mg)溶液,对照组给予0.2mL(只/次)玉米油,经右胸壁中部注射至右肺,每两周处理1次,共4次。处理后观察1年,期间出现呼吸困难时处死大鼠,首次处理后1年处死全部仍存活大鼠,解剖大鼠肺、食管、胃肠道、肝及脑等脏器,观察有无肿瘤形成,并对肿块及全部大鼠的肺组织切片进行苏木素伊红(hematoxylin and eosin,HE)染色分析。结果两组均无大鼠因穿刺注射而死亡。对照组大鼠注射玉米油观察1年仍生存状况良好,处死后均未发现肺及其他脏器肿瘤,1年存活率为100%;模型组大鼠注射3,4-苯并芘-玉米油混合溶液处理后第1只出现呼吸困难者发生于16周,并经组织病理学证实为肺部未分化细胞癌,10只大鼠于处理16周以后至1年之间相继出现呼吸困难,处死后均发现右肺肿块,组织病理学均证实为恶性肿瘤,1只大鼠于处理后26周出现右下肢大腿恶性肿瘤。其余6只大鼠经观察1年仍存活且未出现呼吸困难,其中1只发现肺恶性肿瘤,5只正常。18只接受3,4-苯并芘-玉米油处理中的13只大鼠1年内成功诱发恶性肿瘤,总成瘤率72.22%。其中肺部恶性肿瘤12只(肺部成瘤率为66.67%),组织病理学分类为:2只低分化鳞癌,3只肺腺癌,未分化细胞癌7只,未分化细胞癌占58.33%。结论3,4-苯并芘经胸壁穿刺肺内注射是一种简便可靠的肺肿瘤动物模型的构建方法。更多还原

【Abstract】 Background and objective There is still disadvantage in animal model for lung cancer study, no matter what is xenograft nude mice or rats/mice lung neoplasm induced by carcinogenesis.The purpose of the current investigation is to explore a simple and convenient and reliable method for lung neoplasm animal model. Methods The prepared 36 female Sprague Dawley (SD) rats, with the range from 180 to 220g of body weight, were randomly divided into two groups, each group included 18 rats. In the study group, the rats were given 2mg of 3, 4-benzopyrene soluting in 0.2mL corn oil every two-weekly pulmonary injection for 4 times through right middle-chest percutaneous puncture under control of anaesthesia by pentobarbital sodium i.p. The controls were only given 0.2mL corn oil injection simultaneously. The rats were sacrificed after suffering from dyspnea, and the survived rats were sacrificed at narcotism in 1 year after the first 3, 4-benzopyrene toxicosis. Lung, brain, liver, esophagus and stomach of all rates were anatomized in search of tumor. Results No lung neoplasm was found in the control group within 1-year observation. The earliest dyspnea caused by lung malignant neoplasm was observed in 16 week after the first injection in a rat treated with 3, 4-benzopyrene oil, then 10 rats were sacrificed and found with malignant neoplasm in theirs right lung when the rats suffered from dyspnea, and 1 rat was found a huge tumour in its right lower limb in 26 weeks after treatment. The other 6 rats were sacrificed in 1 year after the first 3, 4-benzopyrene oil treatment, in which 1 rat was found with a malignant neoplasm in its right lung and 5 rats were normal. No tumor was found in brain, liver, esophagus and stomach. Out of these 18 rats, 12 (66.67%) lung malignant neoplasms and 1 limb malignant neoplasm were found within 1 year in the experimental group which yielded a total cancerogenic rate of 72.22% (13/18). The lung neoplasms included: 2 poor-differentitaed squamous cell carcinomas, 3 adenocarcinomas and 7 undifferentiated carcinomas.Conclusion The results suggest that 3,4-benzopyrene pulmonary injection by percutaneous puncture may provide an efficiency method for lung neoplasm model established in rats.更多还原