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目的检测环氧合酶2(COX2)和半胱氨酸蛋白水解酶3(caspase3)蛋白在甲基胆蒽诱导的大鼠肺鳞癌形成过程中的差异表达并探讨其意义。方法采用左肺叶支气管灌注含甲基胆蒽10mg和二乙基亚硝胺0.01ml的碘油溶液诱发Wistar大鼠的肺鳞癌,应用免疫组织化学SP法检测肺鳞癌发生过程中各阶段组织COX2、caspase3的蛋白表达并计算免疫组织化学评分(IHS)。结果实验组多个阶段病变共存的动物标本有80.0%(64/80),其中获取支气管膜上皮增生14份,鳞状化生25份,不典型增生35份,原位癌12份,侵袭癌54份,转移癌15份。正常支气管黏膜上皮偶有COX2弱阳性表达,不典型增生、原位癌及转移癌阶段COX2的IHS逐步增高,差异有高度显著性(均P<0.01)。10例对照组大鼠支气管粘膜上皮细胞中8例(80.0%)有caspase3的阳性表达,不典型增生、浸润癌和转移癌阶段caspase3的HIS逐步降低,差异有显著性(P<0.01、P<0.01、P<0.05)。在对照组和实验组共165例大鼠肺组织病变中,COX2与caspase3呈显著负相关(χ2=106.664,spearman相关系数为-0.678,P<0.01)。结论COX2蛋白上升和caspase3蛋白减少与肺癌的形成密切相关,二者相互作用,共同促进肺癌的发生和侵袭转移。
Objective To investigate the differential expression of cyclooxygenase 2 (COX2) and caspase 3 protein in the process of methylcholanthrene induced lung squamous cell carcinogenesis in rats and its significance. Methods Wistar rat lung squamous cell carcinoma was induced by left lung bronchial perfusion with lipiodol solution containing methylcholanthrene 10mg and diethylnitrosamine 0.01ml. Immunohistochemical SP method was used to detect the expression of tissue in various stages of lung squamous cell carcinoma COX2, caspase3 protein expression and calculate the immunohistochemical score (IHS). Results In the experimental group, 80.0% (64/80) of the specimens coexisted with lesions at different stages. Among them, 14 were bronchial epithelial hyperplasia, 25 were squamous metaplasia, 35 were atypical hyperplasia, 12 were carcinoma in situ, 54, metastatic cancer 15 copies. In normal bronchial mucosa epithelium, the COX2 expression was weakly positive, and the expression of COX2 in atypical hyperplasia and in situ carcinoma was significantly higher than that in the metastatic carcinoma stage (P <0.01). The expression of caspase 3 in 8 cases (80.0%) of bronchial mucosa epithelial cells in 10 control rats was gradually decreased. The expression of caspase 3 in atypical hyperplasia, invasive carcinoma and metastatic carcinoma decreased gradually (P <0.01, P < 0.01, P <0.05). There was a significant negative correlation between COX2 and caspase3 (P <0.01) in the lung tissue of 165 rats in the control group and the experimental group (χ2 = 106.664, spearman correlation coefficient -0.678, P <0.01). Conclusions The increase of COX2 protein and the decrease of caspase3 protein are closely related to the formation of lung cancer. The two interact with each other to promote the occurrence and invasion of lung cancer.