腹腔注射二乙基亚硝胺对大鼠肝肺及痛行为学的影响  

Effects of intraperitoneal injection of diethylnitrosamine on toxicity to liver and lung and visceral pain behavior in rats

作　　者：郭芳 陈建平[2] 贺艳芳[2] 王琳[3] 崔剑[2] 高翔[2] 孙倩倩 罗伟 马成龙 GUO Fang;CHEN Jianping;HE Yanfang;WANG Lin;CUI Jian;GAO Xiang;SUN Qianqian;LUO Wei;MA Chenlong(Department of Anesthesiology,Shanxi Medical University,Taiyuan 030001,China;Department of Anesthesiology,Shanxi Academy of Medical Sciences,Shanxi Dayi Hospital;Department of Pathology,Shanxi Academy of Medical Sciences,Shanxi Dayi Hospital)

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》2018年第9期1006-1012,共7页Journal of Shanxi Medical University

基　　金：山西省应用基础研究计划项目(201601D011120)

摘　　要：目的腹腔注射不同剂量二乙基亚硝胺(diethylnitrosamine,DEN)建立肝癌内脏痛模型,观察建模过程中大鼠肝肺的病理学改变,通过观察大鼠弓背行为对大鼠内脏痛进行评价。方法 60只雄性Wistar大鼠随机分为3组,每组20只,对照组腹腔注射0.9%氯化钠溶液、低剂量组腹腔注射25 mg/kg DEN、高剂量组腹腔注射50 mg/kg DEN。第1次给药开始记为第1周,每周注射2次,4周后改为每周1次,第15周停止注射。从第1周开始,每周对大鼠进行一次内脏痛行为学观察,观察5min内大鼠的弓背程度与弓背时间,得分为二者乘积,得分越高疼痛越剧烈。给药第12,14,16周每组分别处死2只大鼠,20周时全部处死,观察死亡大鼠肝、肺病理学改变。结果在实验过程中,对照组大鼠未出现弓背行为;与对照组相比,低剂量组和高剂量组大鼠随着实验的进行,弓背行为评价得分逐渐增高。实验周期中,对照组大鼠生长发育正常,未出现死亡;与对照组相比,低剂量组在第5周时体质量增长速度变慢,差异均有统计学意义(P<0.05);与对照组相比,高剂量组在第3周时体质量增长速度变慢,第10周时体质量开始下降,差异均有统计学意义(P<0.05)。首次给药后的第20周,低剂量组共意外死亡3只,解剖20只大鼠肝脏在给药18周时可见假小叶结构即肝硬化形成,肺部整个实验周期均呈现炎症改变,肝、肺均未见肿瘤组织;首次给药后的第20周,高剂量组共意外死亡5只,解剖20只大鼠肺部为炎症改变且肺部未见肿瘤组织,病理学观察大鼠肝脏,在给药第14周可见典型的肝癌改变,光镜下肝小叶结果被破坏、病理核分裂像,即高剂量组在14周时建立大鼠肝癌模型。结论不同剂量DEN腹腔注射均对肝肺有明显的损伤;与肺脏相比,肝脏可能对于暴露剂量更加敏感。通过对大鼠弓背行为的观察,随着肝脏病变的进展,大鼠内脏痛逐渐加重。50 mg/kg DEN腹腔注射可成功建Objective To establish a visceral pain model of hepatocellular carcinoma by intraperitoneal injection of different doses of diethylnitrosamine, and observe the changes of toxicity to liver and lung,and evaluate rat visceral pain by observing the rat hunching behavior during the modeling process.Methods Sixty male Wistar rats were randomly divided into 3 groups with 20 rats in each group. The rats were intraperitoneally injected with 0.9% sodium chloride solution in control group, 25 mg/kg DEN in low dose group, and 50 mg/kg DEN in high dose group. All rats were injected twice a week at week 1-4 and once a week at week 5-14.From the first week, the hunching behavior method was used to evaluate the changes of visceral pain in rats. The degree of hunching behavior of the rats was observed within 5 min. The score was the product of the two. The higher the score was, the more severe the pain was. At the week 12, 14, and 16 after administration, 2 rats were sacrificed in each group. All rats were sacrificed at week 20. The liver and lung pathological changes of dead rats were observed.Results During the experiment, rats in control group did not show hunching behavior. Compared with control group, the score of hunching behavior in low-dose group and high-dose group gradually increased as the experiment progressed. During the experimental period, the rats in control group grew normally and did not die. Compared with control group, the body weight in low-dose group increased at week 5, and the body weight slowed down in high-dose group at week 3. At week 10, the body weight began to decline, and the difference was statistically significant（ P 〈0.05）. At week 20 after the first drug administration, 3 rats died unexpectedly in low-dose group. After 20 rats were dissected in low-dose group, the liver cirrhosis was observed in the lobular structure at week 18 after administration, the inflammatory changes of the lungs were observed in the whole experimental period, and no tumor tissues were found in the liver and lun

关 键 词：二乙基亚硝胺 内脏痛行为学 大鼠 肝 肺 

分 类 号：R-332[医药卫生]