自身免疫及其与牙周炎的关系

牙周炎是微生物引起的炎症性疾病,表现为局部牙周组织过度的免疫性炎症破坏。自身免疫可能参与了牙周炎病变过程中复杂的宿主免疫调控反应,其相关机制包括B-1细胞的活化、牙周组织自身抗体的存在、自身反应性T细胞的产生以及牙周致病菌的免疫刺激作用。本文就自身免疫性疾病产生的可能机制、自身免疫与牙周炎的关系作一综述。     

Th17细胞在牙周炎中的研究进展

牙周炎是以牙周组织炎症和牙槽骨破坏为主要特征的慢性炎症性破坏性疾病。近来研究发现Th17细胞存在于牙周炎的病变牙周组织中,提示Th17细胞参与牙周炎的发病过程。本文就Th17细胞在牙周炎发病中的作用进行综述。     

MMP-1及MMP-8在大鼠牙周炎模型牙周组织中的表达与分布

目的:研究不同时期、不同严重程度的大鼠牙周炎模型的牙周组织中MMP-1及MMP-8的表达及分布特征,探讨MMP-1、MMP-8在牙周炎发生发展中的作用。方法:对大鼠牙周炎模型牙周组织标本的石蜡切片进行MMP-1、MMP-8的免疫组化染色,并进行图像定量分析。结果:MMP-1、MMP-8在牙龈炎、牙周炎的牙龈上皮中呈强阳性表达,在牙周炎的牙周组织中,主要在牙周膜成纤维细胞、破骨细胞等细胞中呈强阳性表达,其变化趋势为:由健康牙周组织的弱阳性表达,变为急性龈炎、急性牙周炎的强阳性表达,到慢性牙周炎时期,表达较急性期有所降低。结论:MMP-1、MMP-8在牙周炎症组织中,随着炎症进程呈现不同特征的表达,可能直接参与牙周组织的炎症破坏。     

牙周炎症状态下不同B细胞亚群对破骨细胞调控作用的研究进展

牙槽骨吸收是牙周炎的重要临床表现，持续性骨丧失最终会引起牙齿的松动和脱落，影响患者的生活质量。破骨细胞形成增多及活性增强是牙槽骨吸收的前提，由菌斑微生物所引起的宿主免疫反应对破骨细胞的调控作用是牙槽骨吸收的主要影响因素。B细胞是牙周炎症状态下主要的免疫效应细胞，在炎性牙周组织中占据主导地位。研究表明，牙周炎症状态下不同B细胞亚群对破骨细胞的调控作用不尽相同。文章就浆细胞、记忆B细胞、B-1细胞和调节性B细胞等不同B细胞亚群对破骨细胞的调控作用及其机制予以综述，为牙周炎患者免疫治疗提供有利的线索。     

CRP、ICAM-1、E-selectins在实验性牙周炎大鼠牙周组织中的表达及意义

目的:建立实验性大鼠牙周炎模型,检测C反应蛋白(C reaction protein,CRP)、细胞间粘附分子-1(intercellular adhersion molecule,ICAM-1)、E-选择素(E-selectins)在大鼠牙周组织中的表达及血清中的水平,探讨CRP、ICAM-1、E-selectins在牙周炎发展中的变化。方法:选取纯种6月龄雄性SD大鼠40只,随机分为4组,正常组(A组),4周牙周炎组(B组),8周牙周炎组(C组),12周牙周炎组(D组),每组10只。建立实验性牙周炎动物模型,按计划时间处死实验大鼠,分别检测牙周组织、血清中CRP、ICAM-1、E-selectins的变化。结果:实验性牙周炎随着时间的延长,牙周破坏程度的加深,牙周组织中和血清中的CRP、ICAM-1、E-selectins不断升高,可能进一步加重牙周组织的炎症。结论:CRP、ICAM-1、E-selectins作为牙周炎和心脑血管疾病的共同危险细胞因子,不仅随着牙周炎症的加重而变化,而且能够作为牙周炎导致心脑血管疾病危险因素的证据。     

内质网应激诱导的细胞凋亡在慢性牙周炎中的作用初探

目的:初步探讨内质网应激诱导的细胞凋亡在慢性牙周炎中的作用。方法:利用光学显微镜和透射电镜观察牙周组织中的凋亡细胞,免疫组化染色法检测慢性牙周炎患者及牙周健康者牙周组织中GRP78和CHOP的分布及含量变化。结果:慢性牙周炎组内浆细胞呈现凋亡状态,且GRP78和CHOP在慢性牙周炎组中的阳性表达明显高于正常组(P<0.05)。结论:内质网应激参与了慢性牙周炎的病理生理过程。     

细胞外囊泡在慢性牙周炎疾病进程及诊疗中作用的研究进展

慢性牙周炎是由多种致病因素引起的牙周组织慢性炎症。目前认为,细菌是慢性牙周炎的始动因子,宿主免疫影响牙周炎的发展和结局,其调控机制尚未完全清楚。细胞外囊泡是一类细胞旁分泌产生的亚细胞成分,可携带多种遗传信息介导细胞通信。细胞外囊泡已在肿瘤、心脑血管及免疫性疾病的诊疗中取得重要研究成果,为一些难治性疾病的早期诊断、对因治疗、疫苗设计提供了研究途径。在牙周组织中,牙周膜干细胞、牙龈间充质干细胞、骨髓间充质干细胞、成骨细胞、破骨细胞、免疫细胞及牙周致病菌均可释放不同成分的细胞外囊泡,进行细胞通信和调控,影响慢性牙周炎的疾病进程。本文介绍了牙周组织及牙周致病菌来源的细胞外囊泡特点,综述了细胞外囊泡参与调控慢性牙周炎的研究进展,并展望了细胞外囊泡在慢性牙周炎诊断和治疗中的潜在价值。     

细胞凋亡在糖尿病大鼠牙周炎中参与牙槽骨吸收的实验研究

目的研究糖尿病伴牙周炎牙槽骨破坏机制,初步探讨牙周组织细胞凋亡在该类疾病中所起的作用。方法采用腹腔注射链脲佐菌素（Streptozocin,STZ）制备SD大鼠糖尿病模型,并利用0.2mm不锈钢丝环扎大鼠磨牙颈部制备牙周炎动物模型。观察牙周组织细胞在高血糖状态及正常血糖状态下的组织形态并检测细胞凋亡情况。结果高血糖状态下大鼠牙周炎发病程度明显高于血糖正常大鼠。牙周组织中成骨细胞及牙周膜成纤维细胞凋亡数量高血糖组高于血糖正常组,而破骨细胞数量则相反。结论高血糖状态下牙周炎病损程度较正常血糖状态下严重,牙周组织细胞凋亡参与和加重病程。     

内质网应激诱导的细胞凋亡在慢性牙周炎中的作用初探

利用光学显微镜和透射电镜观察牙周组织中的凋亡细胞,免疫组化染色法检测慢性牙周炎患者及牙周健康者牙周组织中GRP78和CHOP的分布及含量变化。结果:慢性牙周炎组内浆细胞呈现凋亡状态,且GRP78和CHOP在慢性牙周炎组中的阳性表达明显高于正常组(P<0.05)。结论:     

釉基质衍生物对牙周炎症组织中凋亡发生的影响

目的：探讨釉基质衍生物（EMD）对牙龈卟啉单胞菌脂多糖（Pg—LPS）龈沟内注射形成的牙周炎症组织中细胞凋亡的影响。方法：隔日向SpragueDawley大鼠双侧上颌第一及第二磨牙间腭侧龈沟内注射Pg—LPS2wk建立牙周炎模型;牙周炎形成后,龈沟内注射EMD或磷酸盐缓冲液;截取上颌骨标本,行HE染色观察牙周组织破坏情况,TUNEL染色观察牙周组织中细胞凋亡,免疫组织化学染色观察凋亡酶caspase--3和波形蛋白的表达。结果：在大鼠龈沟内注射Pg—LPS后,牙周组织形成明显的炎症和附着丧失;TUNEL染色显示EMD可以抑制Pg—LPS所致牙周组织中的细胞凋亡;免疫组织化学染色显示EMD降低凋亡酶caspase--3的表达,并且促进牙周组织中波形蛋白的表达。结论：EMD可以抑制Pg—LPS所致牙周组织中的细胞凋亡,从而促进牙周组织再生。     

白细胞介素1基因多态性与四川地区慢性牙周炎相关关系的研究

目的检测II-I基因型在不同牙周健康状态汉族人群中的分布,分析III 1等位基因与慢性牙周炎的相关关系。方法选取汉族慢性牙周炎患者182例,检查全口临床牙周附着丧失量,牙周袋深度;同时选取牙周健康对照者89例。棉拭子刮取颊勃膜脱落细胞,用PCR-RFLI,法和PCR法检测II- 1+3953,IIr1A-889,IIr1B-511和IL- 1RN (intron2) VNTR基因型分布。结果重度慢性牙周炎患者组II, 1A-889, IL, l B十3953和ILIlB-511等位基因II以及II- I A-889和II- 1 B-511复合等位基因II , III I B + 3953和IL I B-511复合等位基因H基因频率均显著高于健康对照组 ( P < 0.05) ,II,1RN(intron2) VNTR等位基因的基因型和等位基因频率在各组间的分布无显著性差异(P > 0.05)。结论III 1基因多态性与慢性牙周炎有相关关系,ILII B + 3953,II-IA-889和ILIIB-511等位基因B以及II-IA-889和 II-1B-511复合等位基因II, IIII B + 3953和ILIlB-511复合等位基因II可能是部分慢性牙周炎患者易感性的遗传标志。同时提示II- I基因型在不同地域、不同人种中的分布是不相同的。     

B-1a cells and plasma cells in periodontitis lesions

Background and Objective:  Host response mechanisms in periodontal tissues are complex and involve numerous systems of interactions between cells. The B-cell lineage seems to predominate in chronic periodontitis lesions. The aim of the present investigation was to study the correlation between inflammatory cells and some functional markers in gingival lesions obtained from subjects with severe chronic periodontitis.
Material and Methods:  Thirty-eight Caucasian subjects volunteered to take part in the study. A gingival biopsy from one randomly selected diseased proximal site (probing pocket depth > 6 mm and bleeding on probing positive) was obtained from each patient. Immunohistochemical preparation was used to identify inflammatory cells and functional markers. Correlations between the different percentages of cell markers were analyzed by pairwise correlation.
Results:  B cells (B-1a and B-2 cells) occurred in larger proportions than T cells and plasma cells. A statistically significant correlation was found between the percentage of B-1a cells and plasma cells and between all B lymphocytes and plasma cells. About 60% of B lymphocytes exhibited autoreactive features.
Conclusion:  It is suggested that B-1a cells constitute a significant part of the host response in periodontitis lesions and that plasma cells may develop from both B-2 and B-1a cells.     

The gingival immune response to periodontal pathogens in juvenile periodontitis

A gingival explant culture system was utilized to evaluate the reactivity of local immunoglobulins produced by juvenile periodontitis tissue. Gingival explant culture supernatant fluids were screened, via a standardized dot-immunobinding assay, for antibodies reactive to: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, Eikenella corrodens, Peptostreptococcus micros, Peptostreptococcus anaerobius, Capnocytophaga ochracea, Eubacterium nodatum and Fusobacterium nucleatum and one nonoral microorganism, Porphyromonas asaccharolytica. Of the 75 juvenile periodontitis supernatant fluids tested, the organisms that reacted with the highest numbers of supernatant fluids were E. nodatum (72%) and A. actinomycetemcomitans (49%). More juvenile periodontitis than healthy tissue samples showed supernatant fluid reactivity to P. intermedia, C. ochracea, E. nodatum and P. micros. No significant difference was observed between the juvenile periodontitis group supernatant fluids reactivity and the supernatant fluids of the other periodontal disease groups tested. Cluster analysis revealed the association, as determined by supernatant fluid reactivity, of P. micros and C. ochracea in the juvenile periodontitis group. The data from this investigation are consistent with a hypothesis of multiple possible etiologies of periodontal destruction in juvenile periodontitis and other forms of periodontal diseases.     

程序性死亡配体1负性调控慢性牙周炎的炎症反应

目的 探讨程序性死亡配体1（PD-L1）在慢性牙周炎中是否有表达,以及与不同程度慢性牙周炎的相关关系,为阐明慢性牙周炎的免疫调控机制、临床治疗和预后提供依据。方法 收集健康人和慢性牙周炎患者的牙龈和牙周膜组织。根据临床探测,分为正常对照组、轻度牙周炎组、重度牙周炎组。运用荧光定量聚合酶链反应（PCR）测定不同组牙周组织中PD-L1 mRNA的表达;免疫印迹（Western blot）以及免疫组织化学方法测定不同组牙周组织中PD-L1蛋白的表达。结合临床影像资料,分析PD-L1的差异表达量和不同程度慢性牙周炎的关系。结果 轻度牙周炎组牙周组织中PD-L1的相对表达量显著高于重度牙周炎组（P<0.01）;正常对照组牙周组织中PD-L1的相对表达量与重度牙周炎组牙周组织相比无统计学意义（P>0.05）。结论 PD-L1在牙周组织的表达可负性调控炎症牙周组织损伤。     

Cell-surface proteoglycan expression by lymphocytes from peripheral blood and gingiva in health and periodontal disease.

Cell-surface proteoglycans are involved in lymphocyte migration and activation. This study investigated the expression of syndecan-1, syndecan-4, and glypican in peripheral blood lymphocytes and by lymphocytes in variously inflamed periodontal tissues. Gingival specimens from healthy, gingivitis, or chronic periodontitis sites were stained by means of antibodies against B- and T-lymphocytes and also syndecan-1, syndecan-4, and glypican. Syndecan-1 expression by peripheral blood mononuclear cells (PBMC) from healthy, gingivitis, and chronic periodontitis subjects was assessed by flow cytometry. Syndecan-1 was expressed by B-cells/plasma cells but not T-cells in both gingivitis and chronic periodontitis lesions. Both B-cells/plasma cells and T-cells in gingivitis and chronic periodontitis expressed syndecan-4. Glypican was expressed only by macrophages. Stimulation of PBMC with mitogens and growth factors modulated syndecan-1 expression in both the T- and B-cells. Thus, cell-surface proteoglycan expression by lymphocytes in periodontal inflammation is cell-type-specific and may be modulated by inflammation.     

Influence of anti-CD49f and anti-CD29 monoclonal antibodies on mitotic activity of epithelial cells (HaCaT) and gingival fibroblasts in vitro

A major complication in the treatment of periodontitis marginalis is the reepithelization of periodontal defects inhibiting collagen fiber attachment and periodontal regeneration. In this study we investigated the possibility of a molecular blockade of epithelial mitosis in vitro. Monoclonal antibodies against the VLA-6 laminin receptor subunit alpha6 interrupted interactions between epithelial cells (HaCaT cells) and their extracellular matrix and thus resulted in reduction of proliferation rates by more than 50%. The same effect was observed with anti alpha1-antibodies. In contrast, collagen-producing and -secreting gingival fibroblasts, which play an important role in periodontal regeneration, remained unaffected by the applied anti alpha6 antibodies. Correspondingly, these cells were found to lack VLA-6 laminin receptors. Selective molecular inhibition of epithelial proliferation and apical migration by monoclonal anti alpha6 antibody application may provide an adjuvant periodontitis therapy resulting in an enhanced periodontal regeneration.     

肥胖伴牙周感染小鼠体内B-1a细胞的表达初探

目的:分析肥胖伴牙周感染小鼠体内B-1a细胞的表达变化.方法:建立饮食诱导型肥胖伴实验性牙周感染的小鼠模型,通过免疫组化和蛋白质印迹的方法检测小鼠颌骨和脾脏中CD5、抗Ⅰ型胶原(Col-Ⅰ)抗体、IL-10的蛋白表达量;实时定量PCR检测小鼠颌骨中CD5、抗Col-Ⅰ抗体、IL-10 的mRNA表达量.结果:牙周炎组颌骨中的CD5、IL-10、抗Col-Ⅰ抗体的蛋白和mRNA表达量均显著高于对照组(P<0.001);肥胖组脾脏中的CD5、IL-10、抗Col-Ⅰ抗体的蛋白表达量显著高于标准组(P<0.05);标准伴牙周真性结扎组脾脏中抗Col-Ⅰ抗体的表达量显著高于标准伴牙周假性结扎组(P<0.05).结论:B-1a细胞在肥胖与牙周炎的炎症早期被激活并存在一定的病理意义,这两种炎症状态并没有在病理机制上出现交叉影响.     

实验性牙周炎中调节性T细胞的检测及免疫状态

目的：通过口腔涂抹牙周致病菌加腹腔注射抗原的方法建立一种模拟人类牙周病发病的动物模型,分析调节性T细胞在牙周炎小鼠中的表达情况。方法：采用实体显微镜评价牙周骨吸收的程度,HE染色法观察牙周组织病变的炎细胞浸润情况;FACS检测调节性T细胞在牙周炎慢性炎症期间的表达;实时定量PCR检测牙龈组织中TGF-β1、IL-10mRNA的表达。采用SPSS 17.0软件包对数据进行统计学分析。结果：第4周后,牙周炎组与正常对照组相比,釉牙骨质界至牙槽嵴顶的距离显著增加(P<0.05);牙周组织中大量的炎性细胞浸润,牙周袋加深;TGF-β1、IL-10mRNA的表达水平显著降低(P<0.01);脾脏中调节性T细胞的比率及数量显著少于正常对照组(P<0.05)。结论：牙周炎小鼠中调节性T细胞的数量及功能存在异常,可能与其分泌的免疫抑制性细胞因子表达降低有关。