目的观察核转录因子(nuclear factor-kappa B,NF—KB)特异性抑制剂吡咯二硫代氨基甲酸(pyrrolidine dithiocarbamate,PDTC)对慢性鼻咽炎豚鼠鼻咽黏膜组织浸润炎症细胞增殖与凋亡活性的影响,探讨慢性鼻咽炎在鼻咽癌前病变发生与发展过程中的地位。方法利用细菌病毒联合法建立豚鼠慢性鼻咽炎模型,然后将模型鼠随机分为慢性鼻咽炎对照组和PDTC干预组,并平行设置正常对照组。经药物处理后,取各组动物鼻咽黏膜组织观察病理组织学改变,免疫组化法检测鼻咽黏膜NF-κB p65和增殖细胞核抗原(PCNA)表达活性,末端转移酶介导的dUTP缺口末端标记(TUNEL)技术检测浸润炎症细胞凋亡指数。结果模型组鼻咽黏膜组织浸润炎性细胞NF—κB p65表达活性明显高于正常对照组(P〈O.01),PDTC干预组则明显低于模型组;模型组浸润炎症细胞凋亡时间延长、增殖活性升高,PDTC干预组炎症细胞凋亡活性、增殖水平与正常对照组的差异无统计学意义。结论NF-κB抑制剂PDTC对慢性鼻咽炎黏膜组织中浸润炎症细胞的增殖活性显示明显抑制效应,其机制可能是通过促进靶细胞凋亡活性而发挥效应,提示鼻咽炎有演变为鼻咽癌前病变的潜在风险。
Objective To investigate the effect of NF-κB specific inhibitor pyrrolidine dithiocarbamate (PDTC) on apoptotic and proliferating activities of infiltrating inflammatory cells in nasopharyngeal mucosa among guinea pigs with chronic nasopharyngitis in order to explore the potential association of chronic nasopharyngitis with precancerous lesion in the nasopharynx. Methods The model ofchronic nasopharyngitis was prepared by the combined procedures with a mixed solution of bacteria and virus injected into the nasopharyngeal mucosa of guinea pigs via the approach of nasal cavity at first. Then, these modeling guinea pigs were randomly divided into 2 groups, i.e. modeling group (MG) and PDTC treating group (PTG), supplemented with a healthy controlling group (HCG) as well. Following the treatment of PDTC, all the animals were put into death to take mucosal tissue samples from their nasopharynx. H-E staining procedures were utilized for pathohistological observation on the mucosa, and immunohistochemical assays were taken to determine the expressive activities of NF-κB p65 and proliferating cell nuclear antigen (PCNA), Tdt-mediated X-dUTP nick end labeling (TUNEL) techniques were used to detect the apoptotic index (AI) of inflammatory cells, all determined in the mucosal samples. Results It was shown that the expressive level of NF-κB p65 was significantly higher in the inflammatory ceils in the nasopharyngeal mucosa of MG than that of HCG (P〈0.01), while it was obviously lowered in the mucosal samples of PTG following PDTC treating, when compared with that of MG. On the other hand, the level of AI was markedly reduced in the mucosa of MG; with significantly increased activity of nasopharyngeal epithelial proliferation, as compared with that of HCG. In contrast, the level of AI and the activity of nasopharyngeal epithelial proliferation were found in the mucosa with no statistically significant differences when compared between PTG and HCT (P〉0.05). Conclusions It should be tr