二乙基亚硝胺诱导肝癌小鼠肝组织胶原纤维的变化

摘要

目的：观察胶原纤维在肝癌发生发展过程中的变化及其与癌变的关系。方法饲养清洁健康BALB/c小鼠40只，以30 mg/ml二乙基亚硝胺（DEN）溶液作为饮用水，建立肝癌模型。在开始喂养后的0 w、4 w、8 w、12 w、16 w、20 w和24 w，各处死3只动物，对所取肝脏组织行石蜡包埋切片，采用天狼新红染色，对胶原纤维进行检查。通过Image-Pro Plus 6.0对采集的样本进行光密度积分（IOD）定量，应用SPSS 16.0软件对测得的数据进行ANOVA显著性分析和Student-Newman-Keuls检验。结果小鼠在诱癌剂作用20 w后肝组织发生癌变；在4 w末，小鼠肝组织胶原纤维IOD为（97.610±18.640），明显低于8 w末胶原纤维IOD水平[（377.054±63.668），P＜0.05]；在8 w末，胶原纤维IOD为（377.054±63.668），明显低于12 w末胶原纤维IOD[（625.875±110.846），P＜0.05]；在16 w末，胶原纤维IOD为（847.289±53.473），显著低于20 w末胶原纤维IOD[（1671.301±292.593）， P＜0.01]；在20 w末，胶原纤维IOD为（1671.301±292.593），显著低于24 w末胶原纤维IOD[（3968.450±138.949），P＜0.01]。结论胶原纤维在癌变的整个过程中沉积量逐渐增加，变化明显，可能与肝组织的损伤修复和癌变的扩散密切相关。%Objective To observe the change of collagen in the development of liver cancer in mice with N-nitrosodiethylamine (DEN)-induced liver cancer. Methods Forty BALB/c mice were fed with DEN solution at concentration of 30 mg/ml for routine beverage. Three mice were sacrificed at w 0,w 4,w 8,w 12,w 16,w 20 and week 24 after DEN solution feeding,and the liver tissues were collected each time and embedded in paraffin for pathological examination. The collagen fibers were stained by sirius red staining. The integrated optical density (IOD) of samples were obtained by Image-Pro Plus 6.0. Results The liver cancer was successfully induced at week 20 after DEN intervention as confirmed by pathological check-up;The IOD levels of collagen in liver tis-sues at week 4 was (97.610±18.640),significantly lower than at week 8 [(377.054±63.668),P<0.05];the IOD at week 8 was (377.054±63.668),significantly lower than at week 12 [(625.875±110.846),P<0.05];the IOD at the end of week 16 was (847.289 ±53.473),significantly lower than at week 20 [(1671.301 ±292.593),P<0.01];the IOD at week 20 was(1671.301±292.593),significantly lower than at week 24[(3968.450±138.949),P<0.01]. Con-clusions During the development of liver cancer,the amount of collagen fiber in liver tissues increases gradual-ly,which might be involved in the carcinogenesis.