二亚硝基哌嗪对转基因小鼠TNF受体相关因子2和p16的表达

目的研究二亚硝基哌嗪(N,N′-dinitrosopi- perazine,DNP)对TgN(p53mt-LMP1)/HT小鼠鼻腔和鼻咽黏膜上皮细胞增殖与TNF受体相关因子2(TNF receptor-associated Factor 2,TRAF2)、p16基因表达的影响及两者关系。方法HE染色法观察转基因小鼠组(TC)、转基因小鼠DNP诱导组(T1)和野生小鼠组(CC)、野生小鼠DNP诱导组(CI)鼻腔和鼻咽黏膜上皮细胞增殖特征;免疫组织化学染色法检测小鼠鼻腔和鼻咽黏膜上皮组织中TRAF2、p16基因的表达水平。结果TI、TC、CI和CC组小鼠鼻腔或鼻咽黏膜上皮癌前病变率分别为90%、10%、0和0。与TC、CI和CC组相比,TI组TRAF2基因表达水平显著增高(P<0.01),而p16基因表达水平显著降低(P<0.01);TRAF2和p16基因表达水平在TC和CC组之间的差异亦有统计学意义(P<0.01)。结论TgN(p53mt-LMP1)/HT小鼠鼻腔和鼻咽黏膜上皮细胞增殖活性增加,DNP可提高其增殖活性,而细胞增殖活性增加与TRAF2基因表达水平上调和p16基因表达水平下调密切相关。

Effects of N,N'-dinitrosopiperazine on cell proliferation in nasal and nasopharyngeal epithelia and expression levels of TRAF2 and p16 genes in transgenic mice

OBJECTIVE To investigate the effects of N,N'-Dinitrosopiperazine (DNP) on the cell proliferation of nasal and nasopharyngeal epithelia and the expression levels of TRAF2 and p16 genes in TgN (p53mt-LMP1)/HT transgenic mice and the relationships between them.METHODS The epithelial proliferating characteristics of nasal cavity and nasopharynx in TgN (p53mt-LMP1)/HT cancerous lesion inducing group treated by DNP (TI),TgN (p53mt-LMP1)/HT controlling group (TC), C57BL/6J cancerous lesion inducing group (CI) treated by DNP and C57BL/6J controlling group (CC) were observed for pathological evaluation by HE staining,and the expression levels of TRAF2 and p16 genes in these tissue samples were determined by immunohistochemical methods.RESULTS The occurring rates of precancerous lesions in nasal and/or nasopharyngeal epithelia in TI,TC,CI and CC groups were 90%,10%,0 and 0,respectively (P<0.01). Compared with TC,CI and CC group,the expression levels of TRAF2 gene in nasal and/or nasopharyngeal epithelia of TI group were elevated significantly (P<0.01),and the expression levels of p16 were significantly decreased (P<0.01).The TRAF2 gene and p16 gene expression difference between TC group and CC group was also significant (P<0.01). CONCLUSION It is true that cell proliferating activities are improved in nasal and/or nasopharyngeal epithelia in TgN (p53mt-LMP1)/HT transgenic mice prepared in our laboratory.The possible mechanisms of the improvement of the cell proliferating activities may be closely related to TRAF2 expressing in an up-regulated way and p16 expressing in a down-regulated way.