补体与牙周炎发生发展及其治疗

在牙周炎这一慢性炎症反应过程中,补体不仅可以调解机体防御反应,保护宿主,还可直接作用于免疫细胞或通过调控信号转导通路,协助病原菌进一步感染和破坏牙周组织,最终导致免疫病理性的损伤反应。在免疫炎症反应中,补体不仅可刺激白细胞分泌白细胞介素、肿瘤坏死因子和粒细胞-巨噬细胞集落刺激因子,调节辅助性T细胞和巨噬细胞,促进细胞免疫和T细胞依赖的抗体分泌,增强免疫效应的调节,提高机体免疫力;亦可引起的炎症反应可对组织造成损伤,引起牙周炎。以补体受体拮抗剂干扰补体受体-Toll样受体信号转导通路,有利于机体清除病原菌,达到防治牙周炎的目的。理解补体在牙周炎发生发展中的作用,可为牙周炎治疗探索新途径。     

补体5a及其受体和效应通路与牙周炎的关系

补体（C）5a与其受体（C5aR）结合后,可诱导中．性粒细胞、巨噬细胞等向炎症部位聚集,诱导炎性递质的生成。CD88和C5L2为目前已知的两种C5aR,在中性粒细胞、巨噬细胞和不成熟树突细胞上都有表达,可能促进炎症反应的发生。C5a可能通过细胞外信号调节激酶1、2以及P38促丝裂原激活蛋白激酶通路抑制中性粒细胞程序性死亡发挥促炎作用。抑制C5a与C5aR之间的相互作用,在一定程度上可以抑制中性粒细胞的活化、活性氧的释放以及那基质金属蛋白酶的生成,从而减轻炎症和组织损伤。进一步了解c5a及其受体在牙周炎发生发展中的作用机制可为牙周炎的治疗提供又一新途径。     

细胞自噬在牙周炎中的作用与机制

牙周炎是由牙菌斑生物膜引起的牙周组织的慢性炎症性疾病。细胞自噬是宿主对抗细菌感染的有效武器。近年来研究发现,细胞自噬不仅可以促进感染细胞对细菌和毒素的清除,而且有助于抑制炎症反应,以维持细胞内环境稳态,与牙周炎的发生发展关系密切。本文从细胞自噬与牙周病原菌感染的相互作用,细胞自噬与免疫炎症反应的相互调控,以及细胞自噬与牙槽骨代谢的关系3个方面,对细胞自噬与牙周炎发生发展的关系进行综述,为深入地研究细胞自噬与牙周炎相关机制提供参考,为牙周炎防治的研究提供新的思路。     

细胞自噬在牙周炎中的作用与机制

牙周炎是由牙菌斑生物膜引起的牙周组织的慢性炎症性疾病。细胞自噬是宿主对抗细菌感染的有效武器。近年来研究发现,细胞自噬不仅可以促进感染细胞对细菌和毒素的清除,而且有助于抑制炎症反应,以维持细胞内环境稳态,与牙周炎的发生发展关系密切。本文从细胞自噬与牙周病原菌感染的相互作用,细胞自噬与免疫炎症反应的相互调控,以及细胞自噬与牙槽骨代谢的关系3个方面,对细胞自噬与牙周炎发生发展的关系进行综述,为深入地研究细胞自噬与牙周炎相关机制提供参考,为牙周炎防治的研究提供新的思路。     

Single nucleotide polymorphisms of complement component 5 and periodontitis

Chai L, Song Y‐Q, Zee K‐Y, Leung WK. Single nucleotide polymorphisms of complement component 5 and periodontitis. J Periodont Res 2010; 45: 301–308. © 2009 John Wiley & Sons A/S Background and Objective: Polymorphisms of host defence genes might increase one’s risks for periodontitis. This study investigated whether tagging single nucleotide polymorphisms (SNPs) of the gene encoding complement component 5 (C5) are associated with periodontitis in a Hong Kong Chinese population. Material and Methods: Eleven tagging SNPs of 229 patients with at least moderate periodontitis and 207 control subjects without periodontitis were genotyped using an i‐plexGOLD MassARRAY mass‐spectrometry system. Results: Genotype AG of SNP rs17611 was more prevalent in the group of periodontitis patients than in the controls (54.6% vs. 41.7%, p = 0.007). The haplotype CGCA of the haplotype block consisting of rs1035029, rs17611, rs25681 and rs992670 was significantly associated with periodontitis in a dominant model (p = 0.001). The SNP rs17611 showed high linkage disequilibrium with rs1035029, rs25681 and rs992670. Smoking was also significantly associated with periodontitis (p = 0.006). Conclusion: The tagging SNP rs17611 of the C5 gene and smoking may be associated with periodontitis among the Hong Kong Chinese population.     

Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits experimental periodontitis in rats

Breivik T, Gundersen Y, Gjermo P, Taylor SM, Woodruff TM, Opstad PK. Oral treatment with complement factor C5a receptor (CD88) antagonists inhibits experimental periodontitis in rats. J Periodont Res 2011; 46: 643–647. © 2011 John Wiley & Sons A/S Background and Objective: The complement activation product 5a (C5a) is a potent mediator of the innate immune response to infection, and may thus also importantly determine the development of periodontitis. The present study was designed to explore the effect of several novel, potent and orally active C5a receptor (CD88) antagonists (C5aRAs) on the development of ligature‐induced periodontitis in an animal model. Material and Methods: Three different cyclic peptide C5aRAs, termed PMX205, PMX218 and PMX273, were investigated. Four groups of Wistar rats (n = 10 in each group) were used. Starting 3 d before induction of experimental periodontitis, rats either received one of the C5aRas (1–2 mg/kg) in the drinking water or received drinking water only. Periodontitis was assessed when the ligatures had been in place for 14 d. Results: Compared with control rats, PMX205‐ and PMX218‐treated rats had significantly reduced periodontal bone loss. Conclusion: The findings suggest that complement activation, and particularly C5a generation, may play a significant role in the development and progression of periodontitis. Blockade of the major C5a receptor, CD88, with specific inhibitors such as PMX205, may offer novel treatment options for periodontitis.     

Influence of antiplatelet drugs in the pathogenesis of experimental periodontitis and periodontal repair in rats

Background: Platelets contain an array of biologic mediators that can modulate inflammation and repair processes including proinflammatory mediators and growth factors. Previous studies have shown that periodontitis and periodontal repair are associated with platelet activation. We hypothesized that drug‐induced platelet inactivation may interfere in the processes of inflammation and repair in experimental periodontitis in rats by suppressing the release of biologic mediators from platelets to the site of injury. Methods: To measure the effects on periodontitis, ligatures were placed around first molars, and aspirin (Asp, 30 mg/kg) or clopidogrel (Clo, 75 mg/kg) was given intragastrically once daily for 15 days. Interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and thromboxane A₂ levels were measured by enzyme‐linked immunosorbent assay. To evaluate the effects of antiplatelet drugs on periodontal repair, ligatures were removed after 15 days of periodontitis induction, and Asp or Clo were administered beginning the following day for 15 days. Periodontal repair was assessed by microcomputed tomography. Results: On periodontitis phase, Asp and Clo significantly reduced levels of TNF‐α and Il‐6 (P <0.05), but only Asp decreased thromboxane A₂ (P <0.05). Asp and Clo decreased inflammatory infiltration; however, this reduction was more pronounced with Clo treatment (P <0.05). Histometric analysis showed that Asp and Clo impaired alveolar bone resorption. During the repair phase and after removal of the ligatures, microcomputed tomography analysis demonstrated that treatment with Asp and Clo did not impair alveolar bone repair. Conclusion: Systemic administration of Asp and Clo attenuates the inflammation associated with periodontitis without affecting the repair process when stimulus is removed.     

牙周炎患者红细胞免疫状态的初步分析

目的：通过对牙周炎患者外周血红细胞Ｃ３ｂ受体花环率（ＲＢＣ－Ｃ３ｂＲＲ）和红细胞免疫复合物花环率（ＲＢＣ－ＩＣＲ）的检测,观察青少年牙周炎（ＪＰ）、快速进展型牙周炎（ＲＰＰ）、成人牙周炎（ＡＰ）的红细胞免疫功能状况。方法：采用红细胞酵母菌花环试验方法。结果：ＪＰ、ＲＰＰ患者红细胞免疫粘附力明显低于正常人。ＪＰ、ＲＰＰ患者ＲＢＣ－Ｃ３ｂＲＲ分别为（１０．０３±０．９２）％、（１２．２０±０．９４）％,与对照组（１５．９０±１．７７）％有显著差异（Ｐ＜０．００１,Ｐ＜０．０１）;ＲＢＣ－ＩＣＲ分别为（２７．８９±１．７７）％、（２７．０１±１．７９）％,与对照组（３０．６４±３７）％有显著性差异（Ｐ＜０．０１）;ＡＰ患者ＲＢＣ－Ｃ３ｂＲＲ为（１６．０２±１．２５）％、ＲＢＣ－ＩＣＲ为（３０．０４±１．７３）％,与对照组无显著性差异（Ｐ＞０．０５）。结论：提示ＪＰ、ＲＰＰ的发病机理可能与宿主的红细胞免疫功能低下有关。     

Association of height with inflammation and periodontitis: the Study of Health in Pomerania

AIM: Short stature in adulthood has been associated with increased risk of health problems. Predisposition to inflammatory diseases might be associated with impaired length growth and impose a lifelong inflammatory burden. We tested this hypothesis in a cross-sectional population-based study with respect to periodontitis. MATERIAL AND METHODS: IN 4290 randomly selected subjects from the normal population, we determined anthropometric measures and diagnostic periodontal parameters. Behavioural and environmental risk factors were assessed by interviews and questionnaires. RESULTS: In regression analyses adjusted for age, gender, smoking, diabetes, education, and dental appointments, an inverse association was observed between height and clinical attachment loss. The magnitude of the association was higher in presence of risk factors smoking or diabetes. Odds ratios for smoking were 3.5 (2.2-5.7%, 95% confidence interval) and 2.6 (1.5-4.3%) with the shortest and tallest height quartile, respectively. Figures for diabetes were 1.37 (1.04-1.80%) and 0.97 (0.67-1.39%), respectively. Stratification for age and gender revealed that taller subjects had less periodontitis and decreased concentrations of markers of systemic inflammation than their shorter counterparts. CONCLUSION: This study is the first to associate height with periodontitis concluding that individuals born with a high susceptibility to infectious and inflammatory diseases may suffer from such diseases in childhood whereby the length growth could be impaired. Reaching adulthood, growth comes to a halt but the individual remains susceptible to inflammatory sequelae. Thus, smaller persons pertain a tendency to more severe periodontitis.     

Antimicrobials for the treatment of aggressive periodontitis

Aggressive periodontitis is characterized by a considerable attachment loss over a relatively short period of time. It may be the consequence of either the presence of highly aggressive pathogens or a highly susceptible host. In the first case, the use of antimicrobials should be beneficial in the treatment of those patients. However, due to the organization of the micro-organisms as a biofilm, the increasing incidence of allergies and resistance against antimicrobials and their side-effects, there is still controversy about their benefit in the treatment of periodontal disease. This paper discusses indications for the use of antimicrobials, the substances prescribed and the type of application under the conditions of aggressive periodontitis.     

细胞自噬和炎症反应的相互调控与牙周炎

细胞自噬在真核细胞中广泛存在,其通路可将细胞内衰老损伤的蛋白质和细胞器等细胞成分运送至溶酶体进行降解、清除并循环利用降解后的营养物质。炎症反应是机体应答组织损伤和病原微生物感染等有害刺激的一种保护性反应,过度的炎症反应会导致组织损伤和疾病;而自噬可通过降解DNA、活性氧族等内源性刺激来抑制炎性小体聚集,降解白细胞介素（IL）-1β前体来抑制IL-1β等促炎因子的分泌。牙周致病菌的毒力因子参与牙周组织的破坏,通过其自身携带或释放的脂多糖、肽聚糖和细菌DNA等与宿主细胞的Toll样受体（TLR）等相互作用诱发组织局部炎性细胞浸润和释放炎症因子,导致牙周炎。在牙周局部组织中,病原相关分子模式和损伤相关分子模式通过与TRL或核苷酸结合寡聚化结构域蛋白样受体相互作用,在激活先天免疫反应时诱发自噬,而自噬同时可通过负向调控TLR信号来影响炎症反应。本文就自噬与炎症反应的相互调控作用和自噬与牙周炎的相关性等研究进展作一综述,旨在揭示牙周炎等炎症性疾病的发病机制,为其治疗探索新的途径。     

The role of dental plaque in gingivitis and periodontitis

A dynamic equilibrium between the periodontal microbiota and the host generally results in a clinical state of periodontal health, characterized by minimal inflammatory changes in the marginal gingival tissues. Maintenance of health is most easily achieved by controlling the resident mass of bacteria. In rare instances, control of specific microorganisms may be indicated. Lack of microbial control may lead to an imbalance between the microbiota and the host due to a markedly increased microbial mass and/or increased virulence of the micro-organisms present. Such alterations in the host-parasite equilibrium may result in transient episodes of tissue destruction and, in the long term, to cumulative damage to the periodontal tissues.