COX-2和iNOS在实验性大鼠肺癌发生发展中的表达及其与微血管密度的关系

Cyclooxygenase-2, inducible nitric oxide synthase protein expression and vasculature during experimental rat lung carcinogenesis

目的 探讨环氧化酶 2蛋白 (COX 2 )和诱导型一氧化氮合酶蛋白 (iNOS)在肺癌发生发展中的表达及其与肿瘤血管生成的关系。方法 Wistar大鼠 88只 ,“左肺叶支气管灌注致癌质碘油”法诱发肺鳞癌 ,分批处死 ,获取肺鳞癌发生发展各阶段标本 ,以 10只正常大鼠作为对照。用免疫组化法检测标本中COX 2、iNOS的表达和MVD值。结果 共获取 15 5例病变组织 ,其中 14例支气管粘膜增生 ,2 5例鳞状化生 ,33例不典型增生 ,12例原位癌 ,5 4例浸润癌 ,17例转移癌。不典型增生 (2 .1± 1.9)与鳞状化生 (0 .6± 0 .9)比较、原位癌 (3.7± 2 .4)与不典型增生比较、转移癌 (5 .9± 3.2 )与浸润癌 (3.8± 2 .7)比较 ,COX 2表达评分差异均有显著性 (P <0 .0 1,P <0 .0 5 ,P <0 .0 1)。支气管粘膜增生 (3.7± 2 .1)与正常粘膜 (0 .5± 0 .7)比较、转移癌 (9.1± 4.0 )与浸润癌 (5 .3± 3.7)比较 ,iNOS表达评分差异均有显著性 (P <0 .0 5 ,P <0 .0 1)。原位癌 (31.7±13.3)与不典型增生 (6.2± 4.0 )比较、浸润癌 (4 7.8± 15 .7)与原位癌比较、转移癌 (64 .4± 2 7.7)与浸润癌比较 ,MVD值差异均有显著性 (P <0 .0 1,P <0 .0 1,P <0 .0 1)。COX 2与iNOS表达呈正相关 (r =0 .60 16,P<0 .0 0 1)。MVD与COX 2。

Objective To investigate the expression of cyclooxygenase 2 (COX 2) protein and inducible nitric oxide synthase (iNOS) protein during the experimental lung carcinogenesis in rats, as well as their association with microvessel density (MVD). Methods Diethylinitrosamine and 3 methylcholanthrene were instilled into the left lobar bronchus to induce lung squamous cell carcinoma in 88 Wistar rats, and 10 nomal rats as controls. COX 2, iNOS expression and MVD count of the specimens obtained from the rats were examined by immunohistochemistry. Results A total of 155 specimens of various pathological phase during the carcinogenesis were obtained: 14 hyperplasia, 25 squamous metaplasia, 33 dysplasia, 12 carcinoma in situ, 54 infiltration carcinoma, and 17 metastasis. The immunohistochemical score (IHS) of COX 2 significantly increased in dysplasia, carcinoma in situ and metastasis (P<0.01,P<0.05,P<0.01). IHS of iNOS significantly increased in hyperplasia and metastasis (P<0.05,P<0.01 ). Remarkably increased MVD was found in carcinoma in situ, infiltration carcinoma and metastasis (P<0.01, P<0.01, P<0.01). There was a positive correlation between COX 2 and iNOS (r=0.601 6,P<0.001) expression. Expression of COX 2 or iNOS were remarkably related to MVD count (P<0.01,P<0.01). Conclusion COX 2 and iNOS may play important roles in the carcinogenesis of experimental rat lung squamous cell carcinoma as well as its progress, and it may be associated with stimulating angiogenesis.