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目的探讨环氧化酶2(COX2)对大鼠良性前列腺增生(BPH)的影响及作用机理。方法将成年SD大鼠随机分为正常(A组),BPH模型(B组)和BPH+选择性COX2抑制剂Celecoxib(C组),每组12只。5周后观察各组大鼠前列腺重量和组织学变化,ki67免疫染色及TUNEL染色测定前列腺上皮和间质细胞的增殖和凋亡指数,免疫组化染色及RTPCR法检测COX2及表皮生长因子(EGF),碱性成纤维生长因子(bFGF)和转化生长因子(TGFβ1)蛋白及mRNA表达情况。结果3组大鼠前列腺指数分别为1.70±0.09,1.88±0.17和1.74±0.16,B组显著大于A组和C组(P<0.05);光镜显示B组前列腺上皮细胞增生明显,C组上皮细胞明显萎缩;A组上皮和间质细胞增殖率分别为0.018±0.007和0.007±0.002,B组为0.025±0.006和0.010±0.004,C组为0.017±0.006和0.006±0.003,B组增殖率显著高于A组和C组(P<0.05);3组上皮细胞凋亡率分别为0.015±0.004、0.013±0.003和0.019±0.005,C组较A组和B组显著增高(P<0.05);B组较A组和C组COX2和EGF蛋白及mRNA表达显著增多,TGFβ1表达显著减少(P<0.05),3组间bFGF表达差异无统计学意义(P>0.05)。结论COX2在大鼠BPH组织中表达上调。COX2可能通过调节生长因子表达,影响前列腺细胞增殖及凋亡,参与BPH的发生发展过程。
Objective To investigate the effect and mechanism of cyclooxygenase 2 (COX2) on benign prostatic hyperplasia (BPH) in rats. Methods Adult SD rats were randomly divided into normal group (A group), BPH model group (B group) and Celecoxib (C group), a selective COX2 inhibitor of BPH +, with 12 in each group. The weight and histological changes of the prostate in each group were observed after 5 weeks. Proliferation and apoptosis index of prostate epithelium and stromal cells were detected by ki67 immunostaining and TUNEL staining. The expressions of COX2 and epidermal growth factor (EGF) were detected by immunohistochemistry and RTPCR ), Basic fibroblast growth factor (bFGF) and transforming growth factor (TGFβ1) protein and mRNA expression. Results The prostate index of the three groups were 1.70 ± 0.09, 1.88 ± 0.17 and 1.74 ± 0.16, respectively, which were significantly higher in group B than those in group A and group C (P <0.05). The light microscope showed that the prostatic epithelial cells were significantly proliferated in group B, The cell proliferation rate of group A was 0.018 ± 0.007 and 0.007 ± 0.002 respectively, the group B was 0.025 ± 0.006 and 0.010 ± 0.004, the group C was 0.017 ± 0.006 and the group of 0.006 ± 0.003. The proliferation rate of group B was significantly (P <0.05). The apoptosis rates of epithelial cells in three groups were 0.015 ± 0.004, 0.013 ± 0.003 and 0.019 ± 0.005, respectively, which were significantly higher in group C than those in group A and group B (P <0.05). Compared with group A and group C, the expression of COX2 and EGF protein and mRNA in group B were significantly increased, and the expression of TGFβ1 was significantly decreased (P <0.05). There was no significant difference in bFGF expression between the three groups (P> 0.05). Conclusion COX2 is up-regulated in BPH tissues of rats. COX2 may participate in the pathogenesis of BPH by regulating the expression of growth factors, affecting the proliferation and apoptosis of prostate cells.