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本文研究了aspirin、ibuprofen和sulindac三种不同结构的非甾体抗炎药(NSAID)对大鼠A10血管平滑肌细胞(VSMC)增殖的影响并探讨其作用机制。方法:细胞计数法观察不同浓度的三种NSAID对细胞增殖的影响,乳酸脱氢酶(LDH)释放分析法测定NSAID的细胞毒作用,流式细胞术分析测定细胞周期。结果:aspirin、ibuprofen和sulindac三种NSAID都对A10 VSMC的增殖有明显抑制作用,且其作用是浓度依赖性的,IC_(50)分别是:aspirin为1666μmol/L,ibuprofen为937μmol/L,sulindac为520μmol/L;其抑制作用不是因细胞毒作用引起;三种NSAID对细胞周期的作用不同,ibuprofen(1000μmol/L)和sulindac(750μmol/L)将细胞阻抑在细胞周期的G_1期(从68.7±2.0%上升到76.6±2.2%和75.8±2.2%,P<0.05),而aspirin(2500μmol/L)对处于细胞周期各期的细胞百分率无明显改变;利用有丝分裂抑制剂nocodazole辅助分析,更清楚地检测到了ibuprofen和sulindac在G_1阻抑,而aspirin仍然不引起处于细胞周期各期的细胞百分率的明显改变。结论:aspirin抗A10 VSMC的增殖作用机制与ibuprofen和sulindac两者的作用机制不同,本研究为三种NSAID成为VSMC增殖性疾病的治疗药物提供了理论依据。
In this paper, the effects of aspirin, ibuprofen and sulindac on the proliferation of rat A10 vascular smooth muscle cells (VSMCs) were investigated and the possible mechanism was explored. Methods: The effects of three NSAIDs at different concentrations on cell proliferation were observed by cell counting method. The cytotoxicity of NSAID was assayed by LDH release assay. The cell cycle was analyzed by flow cytometry. RESULTS: The three NSAIDs, aspirin, ibuprofen and sulindac, all inhibited the proliferation of A10 VSMC in a concentration-dependent manner. The IC 50 values were as follows: aspirin 1666 μmol / L, ibuprofen 937 μmol / L, sulindac (520μmol / L) and sulindac (750μmol / L) inhibited the cell cycle in the G_1 phase (from the point of view of the cytotoxicity). The effect of the three NSAIDs on the cell cycle was different from that of ibuprofen 68.7 ± 2.0% to 76.6 ± 2.2% and 75.8 ± 2.2%, P <0.05), while aspirin (2500μmol / L) had no significant change in the percentage of cells in the cell cycle. Assisted by mitotic inhibitor nocodazole It was clearly detected that ibuprofen and sulindac were suppressed in G_1, while aspirin still did not cause a significant change in the percentage of cells at each stage of the cell cycle. CONCLUSION: The mechanism of action of aspirin against A10 VSMC is different from that of ibuprofen and sulindac. This study provides a theoretical basis for the three NSAIDs to be used as therapeutic agents for VSMC proliferative diseases.