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目的 研究参与炎症的重要诱导酶———环氧化酶 2 (COX 2 )和诱导型一氧化氮合酶(iNOS)在大鼠肺鳞癌癌变及进展各阶段的表达情况 ,探讨非甾体类抗炎药 (COX 2表达抑制剂 )和iNOS抑制剂防治肺鳞癌的可能性。方法 Wistar大鼠 80只 ,左肺下叶支气管灌注致癌质碘油 ,分批处死获取肺鳞癌发生发展各阶段标本。免疫组化检测各阶段病变组织COX 2、iNOS的表达并计算免疫组化评分 (IHS) ,各阶段IHS与前一阶段比较。结果 获取支气管黏膜上皮增生 14例 ,鳞状化生 2 5例 ,不典型增生 33例 ,原位癌 12例 ,侵袭癌 5 4例 ,转移癌 17例。支气管黏膜增生、鳞状化生、不典型增生等癌前病变有炎症发生及COX 2、iNOS表达上调。不典型增生、原位癌及转移癌阶段COX 2的IHS增高有显著性 (P <0 .0 1,P <0 .0 5 ,P <0 .0 1) ,支气管黏膜上皮增生及转移癌阶段iNOS的IHS增高有显著性 (P <0 .0 5 ,P <0 .0 1)。COX 2与iNOS表达呈正相关 (r =0 .6 0 16 ,P <0 .0 0 1)。结论COX 2、iNOS在肺鳞癌发生及发展中有一定作用 ,可能是联系炎症与肿瘤发生的分子机制之一 ,非甾体类抗炎药物和iNOS抑制剂化学预防支气管不典型增生、肺鳞癌的发生及肺鳞癌的转移 ,将会取得较好的效果。
Objective To investigate the expression of cyclooxygenase 2 (COX 2) and inducible nitric oxide synthase (iNOS) involved in the carcinogenesis and progression of lung squamous cell carcinoma in rats and to explore the role of non-steroidal Anti-inflammatory drugs (COX 2 expression inhibitor) and iNOS inhibitors may prevent lung squamous cell carcinoma. Methods 80 Wistar rats were infused with carcinogenic lipiodol by bronchus in the lower lobe of lower lung and sacrificed in batches to obtain the specimens of squamous cell carcinoma of lung. Immunohistochemistry was used to detect the expression of COX 2 and iNOS in each stage and to calculate the immunohistochemical score (IHS). The IHS of each stage was compared with the previous stage. Results Bronchial epithelial hyperplasia was obtained in 14 cases, squamous metaplasia in 25 cases, dysplasia in 33 cases, in situ carcinoma in 12 cases, invasive carcinoma in 54 cases and metastatic carcinoma in 17 cases. Bronchial mucosal hyperplasia, squamous metaplasia, dysplasia and other precancerous lesions have inflammation and COX 2, iNOS expression increased. (P <0.01, P <0.05, P <0.01), stage of bronchial epithelial hyperplasia and metastasis of atypical hyperplasia, carcinoma in situ and metastasis stage iNOS IHS increased significantly (P <0.05, P <0.01). There was a positive correlation between the expression of COX 2 and iNOS (r = 0.6016, P <0.01). Conclusions COX 2 and iNOS play a role in the occurrence and development of squamous cell carcinoma of lung, which may be one of the molecular mechanisms of inflammation and tumorigenesis. Non-steroidal anti-inflammatory drugs and iNOS inhibitors can prevent bronchial dysplasia chemically. The occurrence of cancer and lung squamous cell carcinoma metastasis, will achieve better results.