两种选择性环氧化酶-2抑制剂对翼状胬肉成纤维细胞生长影响的对比研究

Investigation of two selective cyclooxygenase-2 inhibitors on HPF

目的:观察两种选择性环氧化酶-2(COX-2)抑制剂对体外培养人翼状胬肉成纤维细胞(HPF)增殖和凋亡的影响,并比较两者作用强弱,寻找辅助治疗和预防翼状胬肉复发的新途径。方法:用0～200μmol/L尼美舒利(nimesulide)和美洛昔康(meloxicam)作用体外培养的HPF,24～96h后观察不同浓度的两种药物对HPF的影响。MTT法及免疫组织化学染色增生细胞核抗原(PCNA)检测细胞生长活性,流式细胞仪测定细胞周期时相变化。结果:在尼美舒利50μmol/L作用24h后,美洛昔康100μmol/L作用24h后均能显著抑制HPF的增殖(P<0.05),呈剂量和时间依赖性。100μmol/L尼美舒利和美洛昔康分别作用48h后,流式细胞仪检测结果发现,药物作用组均出现典型的亚二倍体凋亡峰,G0/G1期细胞百分比上升(P<0.05),S期细胞百分比下降(P<0.05),说明细胞阻滞于G0/G1期。当尼美舒利的浓度在25～200μmol/L,美洛昔康在50～200μmol/L范围内能浓度依赖性地抑制细胞表达PCNA(P<0.05)。结论:两种选择性COX-2抑制剂均能抑制HPF的生长,并诱导其调亡,对COX-2的选择性越高,对HPF的抑制作用越强,尼美舒利的作用强于美洛昔康。

·AIM：To investigate the effect of two selective cyclooxy-genase-2（COX-2）inhibitors（nimesulide and meloxicam）on proliferation and apoptosis of human pterygium fibroblasts（HPF）in culture and search for a new method to prevent the recurrence after pterygium surgery.·METHODS：HPF was incubated with 0-200μmol/L nime-sulide and meloxicam for 24-96 hours.The MTT method was used to assay the biologic activities of the two drugs in different time and different doses.The expression of proliferating cell nuclear antigen（PCNA）in each group was detected by immunohistochemistry method.The cell cycle distribution was measured by flow cytometic analysis.·RESULTS：Administration of 50μmol/L nimesulide or 100μmol/L meloxicam for 24 hours significantly inhibited HPF proliferation in a dose-and time-dependent manner（P〈0.05）.After treated with the two drugs in 100μmol/L for 48 hours,there was significant sub-G1 peak.The number of HPF in G0/G1 phase increased,but in S phase decreased（P〈0.05）,suggesting cells were arrested in G0/G1 phase.The nime-sulide（25-200μmol/L）and meloxicam（50-200μmol/L）inhibited the expression of PCNA in HPF in a dose-depen-dent manner（P〈0.05）.·CONCLUSION：Two selective COX-2 inhibitors can significantly inhibit HPF proliferation and induce its apoptosis.The higher selecti on of COX-2 has the stronger inhibition on the growth of HPF.·