慢性牙周炎合并动脉粥样硬化兔动物模型的抗炎干预研究

Anti-inflammatory intervention for periodontitis complicated with atherosclerosis in rabbits

目的:探讨应用抗生素消除牙周致病菌感染在控制动脉粥样硬化发生、发展中的作用。方法:48只雄性新西兰大白兔随机分为4组,每组12只,A组为对照组,B组为他汀组,C组为抗生素组,D组为联合组(他汀+抗生素)。各组分别按照实验设计进行相应干预处理,至14周末处死动物,分别检测牙周指标、血清中血脂、C反应蛋白(C-reactive protein,CRP)、肿瘤坏死因子(tumor necrosis factor,TNF)-α以及白介-素6(interleukin-6,IL-6)水平,观察降主动脉的病理学改变。结果:C,D组龈沟出血指数、牙周探诊深度低于A,B组(P<0.01),B组略低于A组(P>0.05),C,D组间差异无统计学意义(P>0.05);B,D组血脂低于A组(P<0.01),C组略低于A组(P>0.05),B,D组差异无统计学意义(P>0.05);B,C,D组血清CRP、TNF-α、IL-6均低于A组(P<0.01),D组最低;B,D组内中膜厚度、斑块/内膜面积比低于A,C组(P<0.01),C组低于A组(P>0.05),B,D组差异无统计学意义(P>0.05)。2×2析因设计分析结果显示替硝唑及阿托伐他汀对炎症因子指标具有交互作用(P<0.05)。结论:抗生素治疗慢性牙周炎厌氧致病菌可降低CRP、TNF-αI、L-6等炎症因子水平,可能是防治动脉粥样硬化的机制之一。

Objective To investigate the effect of antibiotics on controlling the development of atherosclerosis by eliminating periodontal pathogen infection by establishing rabbit models of periodontitis and atherosclerosis.Methods Forty-eight male New Zealand rabbits were randomly divided into four groups,group A（control group）,B（statin group）,C（antibiotics group） and D（statin plus antibiotics group）.Each group received the corresponding treatment and all the rabbits were sacrificed after 14 weeks.The contents of periodontal indexes,levels of blood lipid,serum high sensitivity C-reactive protein,tumor necrosis factor-α and interleukin-6 were examined.And the histological changes of aorta were observed.Results Probing depth and sulcus bleeding index were lower in group C and D than those in group A（P0.01）,were slightly lower in group B than those in group A（P0.05）,and there were no significant differences between group D and C（P0.05）.The level of blood lipid was significantly lower in group B and D than that in group A（P0.01）,was slightly lower in group C than that in group A（P0.05）,and there was no significant difference between group B and D（P0.05）.The levels of serum C-reactive protein,tumor necrosis factor-α and interleukin-6 were lower in group B,C and D than those in group A（P0.01）,were the lowest in group D.The intima-media thickness and atheromatous plaque/intima area were lower in group B and D than those in group A and C（P0.01）,were lower in group C than those in group A（P0.05）,and there were no significant differences between group B and D.2×2 factorial design revealed that there was interaction effect between atorvastatin and tinidazole on inflammatory markers（P0.05）.Conclusion Antibiotic therapy for chronic periodontitis anaerobic pathogenic bacteria can reduce the inflammatory indexes as C-reactive protein,tumor necrosis factor-α and interleukin-6,which probably is one of mechanisms of preventing atherosclerosis.