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目的建立云锡矿粉(无氡)诱发F344大鼠肺癌的动物模型,探讨其肺癌发生过程及不同阶段的病理变化。方法190只大鼠随机分为矿粉组(100只)、呋喃甲醛组、生理盐水组及正常对照组(各30只)。除正常对照组外,其他3组分别以质量分数为6%的矿粉悬液、体积分数为2%的呋喃甲醛及生理盐水每次0.2 ml经气管灌注,每周1次,从灌注1周后定期分批处死大鼠,最后处死的1只大鼠染尘100周。光学显微镜及电子显微镜观察矿粉作用下肺组织的形态改变,免疫组化检测高分子和低分子角蛋白确定诱发肺癌的组织类型,Pollak染色观察肺纤维化的进展。结果矿粉组大鼠最早期出现肺部炎症,随着炎症消退见肺间质纤维增生,肺泡及支气管上皮单纯性增生、乳头状增生及鳞状化生,继而出现肺泡非典型腺瘤样增生、鳞状上皮非典型增生,最终出现肺癌。共发生肺癌14例,其中腺癌9例、鳞癌2例、复合癌3例,其他3组均未发生肺癌,矿粉组癌变率与其他3组比较,差异有统计学意义(P<0.01)。鳞状化生及鳞癌也可发生于肺泡并表达高分子角蛋白。矿粉组肺纤维化31例,纤维化程度随矿粉沉着增多而呈进行性加重。结论无氡云锡矿粉具有诱癌性,F344大鼠矿粉诱发性肺腺癌及鳞癌都可发生于肺泡,Ⅱ型肺泡上皮是否是肺腺癌及外周型肺鳞癌的起源细胞值得深入研究。
Objective To establish an animal model of F344 lung cancer induced by tin powder (radon-free) and explore the pathological changes of lung cancer at different stages. Methods Totally 190 rats were randomly divided into mineral powder group (100), furfural group, normal saline group and normal control group (30 rats each). Except for the normal control group, the other 3 groups were treated with 0.2% (by volume) of 2% furfural and 0.2% saline respectively by tracheal perfusion once a week from 6% Rats were sacrificed in batches on a regular basis. One of the rats killed at the end of the experiment was dyed for 100 weeks. The morphological changes of lung tissue were observed under optical microscope and electron microscope. The histological types of lung cancer were determined by immunohistochemical detection of macromolecules and low molecular weight keratins. The progress of pulmonary fibrosis was observed by Pollak staining. Results In the mineral powder group, the earliest pulmonary inflammation occurred. As inflammation subsided, pulmonary interstitial fibrosis, simple alveolar and bronchial epithelial hyperplasia, papillary hyperplasia and squamous metaplasia were observed, followed by atypical adenomatous hyperplasia , Squamous atypical hyperplasia, and eventually lung cancer. A total of 14 cases of lung cancer, including 9 cases of adenocarcinoma, squamous cell carcinoma in 2 cases, 3 cases of complex cancer, the other 3 groups were not lung cancer, mineralized group cancer rate compared with the other three groups, the difference was statistically significant (P <0.01 ). Squamous metaplasia and squamous cell carcinoma can also occur in the alveoli and express macromolecular keratin. 31 cases of lung fibrosis in mineral powder group, the degree of fibrosis increased with the increase of mineral powder was progressive increase. Conclusion Radon-free tin powder has induced cancer, F344 rat lung-induced lung adenocarcinoma and squamous cell carcinoma can occur in the alveoli, type II alveolar epithelial cells is the origin of lung adenocarcinoma and peripheral squamous cell carcinoma cell worth In-depth study.