腹腔注射二乙基亚硝胺诱导肝癌模型中意外死亡大鼠的重要脏器病理学及死因分析  

Analysis of the main organ pathology and death cause during liver cancer modeling induced by intraperitoneal injection of diethylnitrosamine

作　　者：高翔[1] 陈建平[2] 王琳[3] 郭芳[2] 贺艳芳[2] 崔剑[2] 

机构地区：[1]山西医科大学麻醉学系麻醉科,太原030001 [2]山西医学科学院,山西大医院麻醉科 [3]山西医学科学院,山西大医院病理科

出　　处：《山西医科大学学报》2016年第12期1053-1056,共4页Journal of Shanxi Medical University

基　　金：山西省应用基础研究计划项目(201601D011120)

摘　　要：目的分析腹腔注射二乙基亚硝胺(DEN)诱导肝癌模型中大鼠意外死亡的原因。方法 48只Wistar雄性大鼠随机分为实验组和对照组。实验组大鼠腹腔注射0.2 ml DEN溶液(30 mg/ml),每周2次,连续4周后改为每周1次,至14周停止;对照组大鼠腹腔注射0.2 ml生理盐水,注射次数同实验组。每周测量1次大鼠体重,大鼠死亡后剖检肉眼观察心、肺、肝、脾和肾的病理学改变,并在光学显微镜下观察病理学改变。结果实验期间对照组大鼠体重逐渐增加,未出现死亡;实验组大鼠12周开始体重增长速度变慢,与对照组相比差异具有统计学意义(P<0.05),19周时体重出现明显降低,随后体重恢复增长,但直至观察结束始终低于对照组,差异具有统计学意义(P<0.05)。首次给药后的第28周,实验组大鼠共意外死亡18只(18/24,75%),剖检实验组24只大鼠均未发现肿瘤组织。肉眼观察两组大鼠肝无明显异常,实验组在光镜下可见小血管增生、扩张、充血,部分肝细胞水肿,局灶可见慢性炎症细胞浸润。实验组肺表面可见大小不一的灰白色坏死,光镜下可见细支气管管腔中充满脓性分泌物,部分肺泡腔间隔断裂、融合、实变,伴大片脓肿形成。肉眼和光镜下观察两组大鼠心、肾和脾脏,均未见明显异常。结论 DEN腹腔注射可引起大鼠肺脏的明显损伤,是导致建模大鼠意外死亡的重要原因。Objective To analyze the causes of natural death in the modeling of liver cancer induced by diethylnitrosamine（ DEN）.Methods Forty-eight male Wistar rats were randomized into experimental group（ n = 24） and control group（ n = 24）. The rats were injected intraperitoneally with 0. 2 ml DEN solution（ 30 mg / ml） in experimental group and 0. 2 ml normal saline in control group. All rats were injected twice a week at 1- 4 week,and once a week at 5- 14 week. The body weights of rats were measured once a week.The changes of heart,lungs,liver,spleen and kidney were observed after the death with naked eyes and under light microscope. Results During the experiment,the body weight of rats in control group gradually increased,and no one died. In experimental group,the increase of weight slowed down at 12- 18week（ P 〈0. 05）,and the weight significantly reduced at 19 week,and then increased,but the weight was always lower than in control group at 20- 28 week（ P 〈0. 05）. At 28 week after the first administration,18 rats（ 75%） died,and no tumor tissue was found in all 24 rats in experimental group. With the naked eye,no significant abnormalities were observed in liver tissues in two groups. Under the light microscope,the HE staining of liver tissues showed small blood vessel proliferation,expansion,congestion,liver cell edema,and focal chronic inflammatory cell infiltration in experimental group. With the naked eye,there was white necrosis in the lung surface in experimental group. Under the light microscope,the HE staining of lung tissues showed thin bronchial lumen filled with purulent secretion,and fracture,fusion and real change between the some alveolar spaces. Under the naked eye and light microscope,no significant abnormalities were observed in the heart,kidney and spleen in the two groups. Conclusion DEN intraperitoneal injection can cause the lung injuries in rats,which may be an important reason of accidental death.

关 键 词：二乙基亚硝胺 肝癌 动物模型 大鼠 

分 类 号：R735.7[医药卫生—肿瘤]