目的观察氡慢性染毒致大鼠肺组织的病理改变,以及晚期糖基化终产物受体(RAGE)和钙结合蛋白A6(A6,S100A6)蛋白的表达。方法Wistar雄性健康大鼠整体暴露于多功能生态氡室,染毒时间约27个月,染毒结束后观察健康对照组和染毒组大鼠肺组织的病理改变,同时提取大鼠肺组织总蛋白,检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、RAGE和S100A6的表达情况。结果在饲养及染毒过程中,健康对照组和染毒组大鼠各死亡2只,病理切片显示为心衰水肿表现,为自然死亡。存活大鼠病理切片显示肺组织呈充血水肿,炎性反应细胞浸润及肺气肿表现,其中1只大鼠出现肺泡上皮细胞的严重增生性改变,为癌前病变的一种形式。以β-actin为内参,肺组织蛋白表达检测显示,染毒组大鼠PCNA呈高表达(对照组0.0067±0.009,染氡组0.174±0.091),肺组织呈增生性改变,RAGE和S100A6蛋白在染毒组大鼠也呈现高表达(RAGE对照组0.0041±0.006,染氡组0.4372±0.291;S100A6对照组0.069±0.055,染氡组0.493±0.049),其高表达可能与肺组织的癌前病变有关。结论氡慢性染毒可致大鼠肺组织发生癌前病变,并且诱发RAGE和S100A6蛋白的高表达。
Objective To observe the changes in pathology and expression of RAGE (receptor for advanced glycation endproducts) and S100A6 in lung tissue of rats exposed to long-term radon inhalation. Methods Healthy Wistar male rats were exposed to radon in a muhifunctional radon chamber 16 h per day for about 27 month at a cumulative dose of up to 650 WLM. Pathological changes were observed and the protein expression of PCNA(proliferating cell nuclear antigen), RAGE and S100A6 were determined using Western blot. Results In lung tissue of rats exposed to radon, inflammation, emphysema and hyperplasy of alveolar epithelial cells were observed, and expressions of PCNA, RAGE and S100A6 were found to be enhanced(PCNA: 0.0067 ±0.009 in control group, 0.174 ± 0.091 in radon exposed group; RAGE: 0.0041 ± 0.006 in control, and 0.4372 ± 0. 291 in radon exposed group; S100A6 : 0. 069 ± 0. 055 in control, and 0. 493 ± 0.049 in radon exposed group). Conclusion Long-term radon inhalation may cause pathological changes and precancerous change in lung tissues and up-regulated expressions of RAGE and S100A6 proteins.