目的:评估姜黄素（curcumin，CU）、槲皮素（quercetin，QU）及百里香醌（thymoquinone，TQ）单独和联合使用对种植体周围炎主要致病菌［牙龈卟啉单胞菌（Porphyromonas gingivalis，P. gingivalis）和伴放线菌团聚杆菌（Aggregatibacter actinomycetemcomitans，A. actinomycetemcomitans）］生物表型的抑制效果及相关抑制机制。 方法:通过微量稀释法测定CU、QU、TQ单独和联合使用时的最低抑菌浓度和最低杀菌浓度，联合药敏实验测定部分抑菌浓度指数并绘制两种细菌生长曲线；使用酸碱度测定、玻壁法验证药物对细菌的抑制产酸水平、抗黏附能力；以微量稀释法测定药物对细菌的最低生物膜形成抑制浓度、最低清除已形成生物膜浓度；结合扫描电子显微镜观察以上最佳药物对细菌的破坏作用，通过液相色谱‑质谱联用测定最佳药物对细菌的代谢物差异，初步探索其对细菌的作用机制。 结果:CU、QU、TQ单独和联合使用均对P. gingivalis、A. actinomycetemcomitans表现出明显的抑制作用，其中仅CU+TQ对P. gingivalis的抑制呈协同作用，其余对两种菌的抑制呈相加作用；联合用药缩短了P. gingivalis和A. actinomycetemcomitans进入平台期时间，抑制效果存在浓度依赖性；联合用药抑制P. gingivalis和A. actinomycetemcomitans产酸作用（P<0.05），降低了其黏附率（P<0.05）；与单独用药相比，CU、QU、TQ联合用药对抑制P. gingivalis和A. actino‑ mycetemcomitans的单菌种生物膜的形成及生物膜清除的浓度低；联合药物中CU+TQ对致病菌抑制作用最佳，且CU+TQ破坏了细菌细胞膜完整性；CU+TQ对P. gingivalis处理后的差异代谢物有184个（P<0.05），CU+TQ对A. actinomycetemcomitans处理后的代谢物有150个（P<0.05），主要为脂质及类脂分子、有机酸及其衍生物等，代谢通路主要为次生代谢物的生物合成、氨基酸代谢及脂质代谢等。 结论:CU、QU、TQ对种植体周围炎主要致病菌P. gingivalis和A. actinomycetemcomitans的生长活性、产酸能力、黏附能力、生物膜形成等生物表型有明显的抑制作用，且CU+TQ作用最强，并且通过破坏P. gingivalis和A. actinomy‑ cetemcomitans的细胞膜、代谢过程及能量的改变对其起到抑制作用。

Objective:To evaluate the inhibitory effects and related inhibitory mechanisms of curcumin （CU）， quercetin （QU）， and thymoquinone （TQ） used alone and in combination on the biological phenotypes of the main pathogens， Porphyromonas gingivalis （P. gingivalis） and Aggregatibacter actinomycetemcomitans （A. actinomycetemcomitans）， of peri‑implantitis. Methods:The minimum inhibitory concentration and minimum bactericidal concentration of CU， QU， and TQ used alone and in combination were determined by the micro‑dilution method. The fractional inhibitory concentration index was determined by the combined drug susceptibility test， and the growth curves of the two bacteria were plotted. The inhibitory effect of the drugs on the acid production level and anti‑adhesion ability of the bacteria were verified by pH measurement and the glass wall method. The minimum biofilm formation inhibitory concentration and the minimum concentration for eradicating the formed biofilm of the drugs on the bacteria were determined by the micro‑dilution method. The damage of the above optimal drugs to the bacteria was observed by scanning electron microscopy. The differences in metabolites of the bacteria treated with the optimal drugs were determined by liquid chromatography‑tandem mass spectrometry to preliminarily explore their mechanisms of action on the bacteria. Results:CU， QU， and TQ used alone and in combination all showed significant inhibitory effects on P. gingivalis and A. actinomycetemcomitans. Among them， only CU+TQ showed a synergistic inhibitory effect on P. gingivalis， and the inhibitory effects of the others on the two bacteria were additive. The combined use of drugs shortened the time for P. gingivalis and A. actinomycetemcomitans to enter the stationary phase， and the inhibitory effect was concentration‑dependent. The combined use of drugs inhibited the acid production of P. gingivalis and A. actinomycetemcomitans （P<0.05） and reduced their adhesion rates （P<0.05）. Compared to using the drugs alone， the combined use of CU， QU， and TQ had a lower concentration for inhibiting the formation and eradication of the single‑species biofilms of P. gingivalis and A. actinomycetemcomitans. Among the combined drugs， CU+TQ had the best inhibitory effect on the pathogenic bacteria， and CU+TQ damaged the integrity of the bacterial cell membrane. There were 184 differential metabolites （P<0.05） in P. gingivalis after treatment with CU+TQ， and 150 metabolites （P<0.05） in A. actinomycetemcomitans after treatment with CU+TQ， which were mainly lipids and lipid‑like molecules， organic acids， and their derivatives. The metabolic pathways were mainly the biosynthesis of secondary metabolites， amino acid metabolism， and lipid metabolism. Conclusion:CU， QU， and TQ all have significant inhibitory effects on the biological phenotypes such as the growth activity， acid production ability， adhesion ability， and biofilm formation of the main pathogens P. gingivalis and A. actinomycetemcomitans of peri‑implantitis， and CU+TQ has the strongest effect. Moreover， the inhibitory effect is achieve by damaging P. gingivalis and A. actinomycetemcomitans cell membranes， and altering their metabolic processes and energy.

R285

石河子大学第一附属医院青年基金项目（QN202213）；兵团指导性科技计划项目（2023ZD062）；“天山英才”医药卫生高层次人才培养计划资助项目（CZ001224）