口腔扁平苔藓中基质金属蛋白酶及其组织抑制剂的表达

目的 分析基质金属蛋白酶（MMP）2，膜型基质金属蛋白酶1（MT1-MMP），基质金属蛋白酶抑制剂（TIMP）2在口腔扁平苔藓（OLP）中的表达及意义。方法通过免疫组化检测其在OLP中的表达并与口腔鳞状细胞癌（OSCC）及正常口腔黏膜进行比较。结果从正常口腔黏膜（NOM）、非萎缩型OLP，到萎缩型OLP和OSCC3种酶表达依次增加。萎缩型OLP中MMP-2和MTl．MMP的表达明显高于NOM和非萎缩型OLP，与OSCC表达相似。TIMP-2的表达亦随着MMP的增高而增加，但与MMP-2和MT1-MMP相比，其增加量相对较低。结论MMP表达的高低可能成为判断OLP恶变潜能的检测指标之一。     

Th1/Th2细胞在口腔扁平苔藓发病中的研究

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Levels of tissue inhibitor of metalloproteinases-1 and matrix metalloproteinases-1 and -8 in gingival crevicular fluid following treatment with enamel matrix derivative (EMDOGAIN)

The mechanism of enamel matrix derivative (EM D) action on the periodontal wound healing process is not well understood. However, earlier in vitro studies from our laboratory demonstrated that EMD stimulated the proliferation of both periodontal ligament and gingival fibroblast cells. Therefore, the purpose of this study was to further evaluate the effect of EMD on the early wound healing process by assessing the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in gingival crevicular fluid (GCF). Sixteen patients, each of whom had one or two pairs of infrabony defects located contralaterally in the same arch, were included in this clinical trial. Thirty-six infrabony defects were randomly assigned treatment with flap surgery plus EMD or flap surgery plus placebo. At baseline and at 2, 4 and 12 week follow-up evaluation visits, GCF was sampled with paper strips. After determination of GCF volume, TIMP-1, MMP-1 and MMP-8 GCF levels were measured by an enzyme-linked immunosorbent assay. Intragroup analysis: At week 2 following surgery, when compared to baseline all parameters in each study group, except MMP-1, significantly increased (p<0.05). There were no significant differences between 4 or 12 weeks and baseline in either study group. Intergroup analysis: At 4 weeks after surgery, GCF volume and TIMP-1 levels showed a significant decrease (p<0.05) in the EMD group, when compared to the placebo group. MMP-1 levels at weeks 2, 4 and 12, and MMP-8 levels at weeks 4 and 12 were significantly lower (p < 0.05) in the EMD group compared to the placebo group. EMD compared to placebo treated sites demonstrated a more rapid return to baseline levels of TIMP-1, MMP-1 and MMP-8. These findings suggest that treatment with flap surgery and EMD, compared to flap surgery with placebo, accelerated healing at an earlier stage of wound healing following surgery.     

Ets-1在口腔扁平苔藓中的表达研究

目的 :分析Ets 1(E2 6transformation specific)在口腔扁平苔藓 (OLP)的表达及意义。 方法 :采用免疫组化ABC法检测Ets 1蛋白在 2 0例口腔扁平苔藓和 8例正常口腔黏膜组织中的表达。结果 :70 % (14 /2 0 )的口腔扁平苔藓病例中Ets 1呈阳性表达 ,明显高于正常黏膜组织 ,两者比较有显著性差异 (P <0 .0 5 )。阳性表达率在溃疡型OLP与斑块型OLP间亦有显著性差异 (P <0 .0 5 ) ,并与病程相关 (P <0 .0 5 )。结论 :Ets 1在口腔扁平苔藓中过表达并与其发病有关。     

ALDH1在OLP和LK组织中的表达及其意义

目的：通过检测干细胞标记物ALDH1在口腔扁平苔藓（OLP）和白斑（LK）中的表达水平,评价其与癌变的关系。方法：采用免疫组织化学SP法检测ALDH1在10例正常口腔黏膜,30例OLP,60例LK,10例口腔鳞癌（OS－CC）中表达水平;再检测ALDH1在30例癌变与30例未癌变LK中的表达差异。结果：ALDH1在正常口腔黏膜中不表达,在OLP、LK和OSCC中的表达率分别为26．7％,63．3％和90．0％（P＜0．05）;ALDH1在未癌变和癌变LK中的表达率分别是43．3％和83．3％（P＜0．01）。结论：ALDH1与口腔黏膜恶性潜能程度相关,可能是预测癌变的分子标记物。     

DNA ploidy in oral lichen planus,determined by image cytometry

J Oral Pathol Med (2010) 39 : 206–211 Background: The objective of this study was to use image cytometry to determine the degree and frequency of DNA ploidy in biopsies of reticular and atrophic‐erosive oral lichen planus and to analyze 14 karyometric measurements of the nuclei of epithelial cells from each specimen. Methods: A total of 40 slides were analyzed, each of them representing one biopsy of one oral lichen planus (OLP) lesion from each one of the 40 patients (cases) studied. Specimens were embedded in paraffin and comprised 20 slides of reticular oral lichen planus (group R) and 20 slides of atrophic‐erosive oral lichen planus (group AE). Results: Group R, the reticular lichen samples, had 18 diploid cases and two aneuploid cases. Group AE, the atrophic‐erosive lichen samples, had 10 diploid cases, one tetraploid case, and nine aneuploid cases. Of the 14 karyometric measurements of the nuclei of OLP epithelial cells analyzed, the group R mean values for mean density and minimum density were significantly greater than the group AE mean values, and mean roundness in group AE was significantly greater than in group R (t‐test: P < 0.05). Conclusions: The most common degree of DNA ploidy in OLP lesions was diploidy. Comparing the two groups (chi‐square test of association P = 0.021) demonstrated that diploidy was associated with the reticular clinical form of OLP, while aneuploidy was associated with the atrophic‐erosive clinical form of oral lichen planus.     

Mast cell expression in oral lichen planus: A systematic review

Lichen planus is a common chronic, inflammatory, immune‐mediated mucocutaneous disorder affecting the skin and mucosa. The role of mast cells in the genesis of lichen planus has been debated. Establishing a definitive part played by mast cells and its degranulation would possibly provide a permanent, cost‐effective treatment modality for oral lichen planus (OLP). This review aims to study the expression of mast cells qualitatively and quantitatively in OLP. The research questions were framed to assess the mast cell count, localization within the epithelium basement membrane zone and degranulation of mast cells. We performed a systematic search of PubMed, Medline, Cochrane and Web of Science. We found a total of 120 studies from which 12 were found suitable for the review. There is a marked increase in the number of mast cells in OLP. The mast cells were seen in increased numbers in the epithelial and connective tissue junction at areas of basement membrane disruption. There was also an increase in the degranulation of mast cells. It is evident that there is an increase in the mast cell number in lichen planus and its subsequent degranulation.     

The frequency of Candida in oral lichen planus

ABSTRACT – Histologic material of typical lichen planus lesions from 43 patients was studied. Two sections of each specimen were stained with hematoxylin-eosin and 10 sections by the PAS method. Only 1 of 43 biopsies was invaded by Candida, and hyphae were present in all of the 10 PAS-stained sections of this case. The results show that oral lichen planus has a considerably lesser susceptibility than oral leukoplakia to invasion by Candida albicans.     

OLP组织中Smad7蛋白的表达研究

目的:检测Smad7蛋白在口腔扁平苔藓(OLP)组织中的表达及分布,探讨其在OLP发病机制中的作用。方法:采用免疫组化SABC法,用Smad7兔抗人多克隆抗体检测60例OLP病变组织及10例正常口腔黏膜组织中Smad7蛋白的表达及分布。结果:Smad7在OLP病变组织有明显的阳性表达,而在正常口腔黏膜组织中阴性表达(P<0.05)。结论:Smad7蛋白在OLP病变组织中高表达,其在OLP发病机制中有重要作用。     

Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus

ObjectiveOral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases.MethodsMetabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease.ResultsIn total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP.ConclusionThe dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease.     

The high expression level of programmed death‐1 ligand 2 in oral lichen planus and the possible costimulatory effect on human T cells

J Oral Pathol Med (2011) 40 : 525–532 Background: Oral lichen planus (OLP) is a T‐cell‐mediated chronic autoimmune disease whose precise etiology is unknown. The recently identified costimulatory programmed death‐1 (PD‐1) molecule and its ligands, PD‐L1 and PD‐L2, have been identified as CD28‐B7 family molecules and constitute a regulatory pathway of potential therapeutic use in immune‐mediated diseases. Methods: We examined the expression of two ligands of PD‐1 at both the protein and gene level in the focal mucosa and peripheral blood of OLP patients using immunohistochemistry and real‐time PCR. Next, we used the PD‐L2.Ig fusion protein and observed its effects on T cells, which were co‐cultured with IFN‐γ‐treated keratinocytes (KCs) in the presence of PHA. Results: We found that the expression of PD‐L2 at both the gene and protein level was statistically different in peripheral blood and local lesion tissue of patients with OLP compared to the normal controls. The proliferation ability of T cells and the expression level of IFN‐γ in the supernatant of the above co‐culture model were significantly augmented (P < 0.05). PD‐L2.Ig fusion protein significantly aggravated the apoptosis of T cells, inhibited the proliferation of T cells and decreased the release levels of IL‐2 and IFN‐γ in the model (P < 0.05). Conclusion: These data show that the increased expression of PD‐L2, as a costimulatory molecule, may have an important modulatory function on the local immune responses of OLP in vivo.     

The role of histopathological characteristics in distinguishing amalgam-associated oral lichenoid reactions and oral lichen planus

OBJECTIVES: To identify histological features that distinguish amalgam-associated oral lichenoid reactions (AAOLR) from oral lichen planus (OLP). METHODS: Oral pathologists provided their opinion as to the possibility of distinguishing AAOLR and OLP histologically, the features important in distinguishing AAOLR from OLP and the diagnosis of 12 AAOLR and 12 OLP cases including the features that drew them to their conclusion. RESULTS: There was considerable variation between pathologists in their ability to distinguish the AAOLR and OLP cases. The sensitivity and specificity for histological diagnosis were 40% and 32% respectively. There were four features that were used most commonly to discriminate between AAOLR and OLP: an inflammatory infiltrate located deep to superficial infiltrate in some or all areas; a focal perivascular infiltrate; plasma cells in the connective tissue and neutrophils in the connective tissue. Each was independently predictive of AAOLR or OLP (P < 0.028). CONCLUSIONS: This study confirms the uncertainty of the diagnostic histological differences between AAOLR and OLP. Distinguishing these conditions should not rely on histology alone, but should be based on a synthesis of all available information including history, examination, histopathology and skin patch testing.     

细胞凋亡相关蛋白Bcl-2对OLP病损区淋巴细胞聚集的影响

目的:探讨凋亡相关蛋白Bcl-2在口腔扁平苔藓(OLP)病变中的生物学行为及对OLP皮损中浸润淋巴细胞聚集、分布的影响,进一步了解OLP的发病机制。方法:采用免疫组织化学检测法,与正常口腔黏膜对照,观察分析25例OLP皮损中Bcl-2蛋白的表达水平及淋巴细胞聚集、分布。结果:OLP病损区T细胞中Bcl-2过度表达,固有层淋巴细胞异常克隆、聚集,浸润增加。结论:OLP病损区中T细胞高密度聚集可能是Bcl-2诱导的局部淋巴细胞过度增殖后关联反应。     

Induction and upregulation of adhesion receptors in oral and dermal lichen planus

The expression pattern of well-defined cell surface adhesion receptors called VLA-family, LFA-1 and ICAM-1 was determined semiquantitatively in biopsies of oral (n = 12) and dermal lichen planus (n = 5) and compared to normal uninvolved human oral mucosa (n = 12) and skin (n = 12) using an indirect immunoperoxidase technique. In both oral and dermal lichen planus, an induction of the beta 1-integrins VLA-1 and VLA-3 and an upregulation of VLA-6 was found in T cells infiltrating the basement membrane zone. These cell surface molecules function as receptors for collagen, fibronectin and laminin. A focal induction of ICAM-1 on basal keratinocytes could be detected at sites of intramucosal T cells. These results suggest that investigated adhesion receptors are crucially involved in the aggregation of T cells in both conditions. Further investigations have to be done to determine the functional role of these adhesion receptors in lichen planus.     

生物制剂在口腔扁平苔藓治疗中的应用

口腔扁平苔藓(oral lichen planus,OLP)是一种病因不明、与自身免疫密切相关的慢性炎性疾病.皮质类固醇和免疫抑制剂是治疗OLP的常用药物,但部分OLP患者表现为不敏感或治疗抵抗.有研究提示生物制剂对治疗常规药物治疗不敏感或抵抗的OLP患者显示出优势.该文就治疗OLP生物制剂的种类、机制、疗效、预后及不...     

STIM1在口腔扁平苔藓患者中表达的研究

目的：通过观察基质相互作用分子1（stromal interaction molecule 1,STIM1）在口腔扁平苔藓（oral lichen planus,OLP）患者外周血淋巴细胞中的表达,探索 OLP的发病机制。方法：采用实时定量 RT-PCR的方法,检测37例 OLP 患者及17例健康成人外周血淋巴细胞中的 STIM1基因表达水平;采用 Western blot法检测上述对象外周血淋巴细胞中的 STIM1蛋白表达水平。结果：糜烂型和非糜烂型 OLP患者中 STIM1基因和蛋白的表达水平均高于对照组,且差异有统计学意义（P＜0．01）;但糜烂型和非糜烂型 OLP患者组间表达的差异均无统计学意义（P＞0．05）。结论：STIM1在 OLP 外周血淋巴细胞中高表达,通过对淋巴细胞的免疫调控参与了 OLP的发病过程。     

口腔扁平苔癣患者组织中一氧化氮及一氧化氮合酶的检测

目的：了解一氧化氮（NO0及一氧化氮合酶（NOS）在口腔扁平苔藓（OLP）发病中的作用。方法：选择OLP患者（其中糜烂型12例，非糜烂型18例）及健康献血员各30例，分别检测局部病变组织和正常对照组织中NO含量（硝酸还原酶法）和NOS活性（化学比色法），所得数据采用配对t检验进行统计学处理。结果：NO值，OLP组高于正常对照组（P＜0．05），糜烂型虽高于非糜烂型（P＞0．05），但无统计学差异；NOS，OLP组明显高于正常对照组（P＜0．01），糜烂型也明显高于非糜烂型（P＜0．01）。结论：在OLP发生发展的不同阶段，NO和NOS呈动态变化，过多的NO含量及NOS活性增加与OLP发生发展有关。本研究提示，NO生成抑制剂可作为一种新型药物，用于辅助治疗OLP。