家兔颊黏膜上皮癌前病变模型制备及药物逆转超微结构观察

目的 建立鳞状上皮癌前病变动物模型,筛选癌前病变逆转药物,观察家兔颊黏膜上皮在此过程中超微结构变化.方法 12只家兔为空白对照组,48只家兔为实验组,将含有致癌剂二甲基苯并蒽(dimethyl-benzanthracene,DMBA)溶液及药膜涂抹或贴附于口腔颊黏膜；给药16周后做病理组织学检查及电镜扫描.再随机选取实验组中的32只进行药物逆转实验,12周后行病理组织学检查及电镜扫描.结果 涂抹二甲基苯并蒽16周后,家兔颊黏膜粗糙充血,局部可见增厚白斑,Ⅱ-Ⅲ 级不典型增生发生率为64.6％(31/48).不典型增生细胞排列紊乱,细胞核内异染色增多,线粒体水肿.药物逆转实验第12周,全反式维甲酸组病变进展率低,与对照组相比差异有统计学意义,康莱特组可见病变逆转,但与对照组相比差异无统计学意义.结论 应用DMBA可成功制备鳞状上皮癌前病变；全反式维甲酸(alltransretinoic acid,ATRA)可有效逆转癌前病变.

Preparation of rabbit buccal mucosa epithelial precancerous lesion model and observation of drug-reversed ultra-microstructure change in rabbit buccal epithelium

Objective To establish the rabbit model of squamous epithelial precancerous lesion and observe the ultra-microstructure change of rabbit buccal mucosa epithelium in order to screen its revering drugs.Methods Sixty rabbits were divided into control group(n=12) and experimental group(n=48).Pathological histology examination and electron microscopy were performed for the buccal mucosa of rabbits in experimental group 16 weeks after a solution and a drug membrane containing the carcinogen of dimethyl-benzanthracene(DMBA)were sprayed or pasted on it.Thirty-two rabbits were randomly selected from experimental group to carry out drug-reversing experiments 12 weeks after a solution and a drug membrane containing the carcinogen of DMBA were sprayed or pasted on it.Results Sixteen weeks after the rabbits were exposed to DMBA,their buccal mucosa became rough and congested with thickened local leukoplakia and Ⅱ-Ⅲ atypical hyperplasia in 64.6%(31/48) of the rabbits in experimental group.Disarranged atypical hyperplasia cells and edematous mitochondria were found in nuclei.Twelve weeks after drug-reversing experiment,the progressive rate of precancerous lesion was lower in rabbits exposed to all-transretinoic acid(ATRA) than in controls.Although Kanlaite could reverse the precancerous lesion but no significant difference was observed between those exposed to it and controls.Conclusion Squamous epithelial precancerous lesion model can be induced by DMBA and effectively reversed with ATRA.