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大鼠肺癌发生发展动物模型的构建 被引量:26

Establishment and significance of animal model about occurring and developing in rats lung carcinoma
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摘要 目的 :探讨人类肺癌的发病机制 ,构建肺癌的动物模型 ,以了解肺癌发生发展的全过程。方法 :采用煤焦沥青 (CTP)支气管灌注的方法 ,诱发大鼠肺癌动物模型。初断乳Wistar大鼠 71只 ,饲养 4周后体重 12 0~ 2 0 0g ,随机分为 3组。实验组Ⅰ 31只 ,灌注中温CTP生理盐水悬液 ,累计灌注量为 192mg ;实验组Ⅱ 15只 ,灌注中温CTP玉米油悬液 ,累计灌注量为 2 5 6mg ;对照组 2 5只 ,灌注炭粉生理盐水悬液 ,累计灌注量为 192mg。 3种悬液质量浓度均为 16 0g/L ,沥青和炭粉分散度均为粒径小于 10 μm者大于 94% ,各加入少量青霉素。每次灌注量均为 0 .2ml,每次间隔 7~ 10d ,实验组Ⅰ和对照组灌注 6次 ,实验组Ⅱ灌注 8次。测定中温CTP苯溶物 (BSF) ,上街沥青为 0 .34 64g/L ,安钢沥青为 0 .35 75g/L。实验组Ⅰ和对照组于染毒后第 3,6 ,13个月 ,实验组Ⅱ于染毒后 6个月系列宰杀。宰杀前X光胸部前后位摄片 ,见可疑病变者宰杀。标本用中性福尔马林固定 ,切片 ,HE染色 ,光镜观察。结果 :实验组Ⅰ染毒第 3个月宰杀 12只均未见异常病理改变 ;第 6个月宰杀 7只 ,5只见鳞状上皮化生 ,其中 3只见不典型增生 ,1只出现原位癌 ;第 13个月宰杀 12只均见鳞状上皮化生 ,其中 4只见不典型增生 ,3只出现原位癌 ,2只鳞癌 ,1只类癌。实? Aim: Lung carcinoma is the most frequent cancer in the world, and today its incidence is rapidly rising. It is forecasted that lung carcinoma in the 21 century is the leading disease in the epidemic of carcinoma. Since its mechanism remains poorly understood, diagnosis and treatment effect are relatively bad, its incidence and dead rat are very high. So it is very important to study the mechanism causing lung carcinoma. Coal tar pitch (CTP) mainly comprises polycyclic aromatic hydrocarbons (PAH) and PAH in the environment is connected with human lung cancer. Both animal experiment and epidemic research have demonstrated that CTP can cause lung cancer. To explore the whole process of lung cancer occurring and developing, we took the bronchia perfusion method to place a premium on animal model of rats lung carcinogenesis based on our research and other scholars studies. Methods: The 71 Wistar rats which just stopped eating milk were randomly divided into three groups, whose weight were from 120 g to 200 g after being bred for four weeks. Experiment group I containing 31 cases were perfused by mild temperature CTP suspending in normal saline, experiment group II containing 15 cases were perfused by mild temperature CTP suspending in corn oil,and control group containing 25 cases were perfused by charcoal powder in normal saline. The concentration of three suspending solutions were all 160 g/L, the dispersion degree of pitch and charcoal powder which diameter were less than 10 μm were more than 94%, and infused less penicillin. The concentration of benzene solving flour (BSF) in group I pitch was 0.346 4 g/L, 0.357 5 g/L in group II pitch. Perfusion quantum was 32 mg each time; perfusion interval was from 7 days to 10 days each time. The cumulated perfusion quantum of experiment group I, II and control group were separately 192 mg, 256 mg and 192 mg. Experiment group I and control group were slain in the third, sixth, thirteenth month after having caught toxin,and experiment group II were slain in the sixth month after having caught toxin. Before slain, X ray sternum was taken from front to back, if suspect pathological changes were found, then slain. Samples were secured by mild formalin, sliced up, HE dyed, observed under light lens. Results: ①Weight changes of the three groups were similar. it was shown that CTP dosage had less effect on growth . Those who died naturally lose their weight, exhausted,most of them caught lung carcinogenesis or united infection.②Tumor lay lung surface.The diameter was about 0.5 cm, irregularly nodular shape, velvet surface, clear boundary, no envelope, hard texture, hoariness.③ Observed under light lens, and among the experiment group I, 12 mice were slain in the third month and change in pathology. 7 mice were slain in the sixth month, 5 mice were found squamous epithelium, including 3 atypical hyperplasia and one of three was found primary carcinoma. In the thirteenth month, 12 mice were all found squamous epithelium, including 4 atypical hyperplasia and three of four were found primary carcinoma, two of three belonged to squamous carcinoma, one belonged to genus carcinoma. In the experiment group II, 15 mice were all found squamous epithelium in the sixth month after having caught toxin, including 13 atypical hyperplasia, 7 cases primary carcinoma, 6 cases squamous carcinoma. In control group, pathologic changes were not found all the time. Conclusion: It was successfully placed a premium on rats lung carcinoma by CTP. The developing process was: normal bronchial epithelium squamous epithelium →epithelial hyperplasia→atypical hyperplasia→primary carcinoma→endosmosis carcinoma(squamous carcinoma). It is helpful to reckon the dosage causing lung carcinoma, which human may contact analogue causing carcinoma, and the time of each pathologic phase ,according to CTP perfusion quantum and accurate record of when lung carcinoma happened in each pathologic phase, and it provided good experiment datum to explore the mechanism causing human lung carcinoma.
出处 《河南医科大学学报》 2000年第3期232-235,F004,共5页 Journal of Henan Medical University
基金 河南省自然科学基金资助项目!9840 2 0 3 0 0
关键词 多环芳烃 支气管灌注 动物模型 肺肿瘤 coal tar pitch polycyclic aromatic hydrocarbon bronchia perfusion disease model,animal lung cancer rats
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  • 1M. W. A. C. Hukkelhoven,A. M. Bronkhorst,A. J. M. Vermorken. Covalent binding of BP-metabolites to DNA of cultured human hair follicle keratinocytes[J] 1985,Archives of Toxicology(1):6~12

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