THE DEVELOPMENT OF A NEW CLINICAL PARAMETER FOR DIAGNOSIS OF PERIODONTAL DISEASES AND THE NEW DRUG DESIGN

牙周疾病诊断新临床参数的开发和新药物设计

• 批准号: 02557072
• 负责人: YAMAMOTO Kenji
• 金额: $ 11.2万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02557072/
• 关键词: PERIODONTITIS; GINGIVITIS; CATHEPSIN B; CATHEPSIN H; CATHEPSIN L; CATHEPSIN G; MEDULLASIN; GINGIVAL CREVICULAR FLUID; 顆粒球セリンプロテア-ゼ; カテプシンG; プロテア-ゼ

Although a number of clinical parameters are now used for diagnosis of periodontal diseases, there exists the practical difficulty as to which parameters should be used to assess the rate of progress of the disease, the present disease activity and the need for treatment. is generally accepted that analysis of gingival crevicular fluid (GCF) can provide information of association between specific metabolic change and disease status and that a variety of proteolytic enzymes in GCF play an important role in pathogenesis of periodontal disease. The present work was designed to clarify the roles of lysosomal proteinases including cathepsins B, H, L, D, G, and medullasin in pathological destructive process of periodontal tissues and to put the knowledge of the GCF levels of these enzymes to practical use for diagnosis of periodontal diseases. For this purpose, we prepared the specific antibodies to each enzyme purified from human sources and determined the levels of enzymes in GCF from chronic adult periodontitis patients and experimental gingivitis subjects by enzyme immunoassay. The results indicate that the cysteine proteinases cathepsins B, H, and L are selectively released into gingival crevices at a relatively mild stage of periodontitis and their levels in GCF are positively correlated with the severity of the disease. However, no significant amounts of these enzymes are found in GCF from experimental gingivitis subjects. The serine proteinases medullasin and cathepsin G in GCF are also shown to increase with the severity of periodontitis and to decrease by periodontal treatment. Interestingly, large amounts of medullasin was detected in GCF from experimental gingivitis subjects. The results indicate that these lysosomal proteinases participate in the progression of periodontitis and that the dynamics of these enzymes in GCF is useul for determining the present disease activity and the disease progression.

虽然目前有许多临床参数用于牙周病的诊断，但实际困难在于应该使用哪些参数来评估疾病的进展速度、目前的疾病活动和治疗的必要性。人们普遍认为，龈沟液（GCF）的分析可以提供特定代谢变化与疾病状态之间的关联信息，龈沟液中多种蛋白水解酶在牙周病的发病机制中起重要作用。本研究旨在阐明溶酶体蛋白酶包括组织蛋白酶B、H、L、D、G和髓质酶在牙周组织病理破坏过程中的作用，并将这些酶的GCF水平的知识用于牙周疾病的诊断。为此，我们制备了针对人源纯化的每种酶的特异性抗体，并采用酶免疫法测定成人慢性牙周炎患者和实验性牙龈炎受试者GCF中酶的水平。结果表明，半胱氨酸蛋白酶组织蛋白酶B、H和L在牙周炎的相对轻度阶段选择性释放到龈缝中，其在龈沟中的水平与疾病的严重程度呈正相关。然而，在实验性牙龈炎受试者的GCF中没有发现大量的这些酶。GCF中的丝氨酸蛋白酶髓质酶和组织蛋白酶G也随着牙周炎的严重程度而增加，并因牙周治疗而减少。有趣的是，在实验性牙龈炎受试者的GCF中检测到大量的髓质酶。结果表明，这些溶酶体蛋白酶参与牙周炎的进展，这些酶在GCF中的动态变化对确定当前疾病的活动性和疾病的进展是有用的。

项目成果

K.Kunimatsu, K.Yamamoto, E.Ichimaru, Y.Kato, and I.Kato: "Cathepsins B,H and L activities in gingival crevicular fluid from chronic adult periodontitis patients and experimental gingivitis subjects." J.Periodont.Res.25,No.2. 69-73 (1990)

K.Kunimatsu、K.Yamamoto、E.Ichimaru、Y.Kato 和 I.Kato：“慢性成人牙周炎患者和实验性牙龈炎受试者的龈沟液中组织蛋白酶 B、H 和 L 的活性。”

H.Nakanishi, K.Ukai, T.Nakagawa, S.Watanabe, O.Kamata, and K.Yamamoto: "Enhancement of NMDA receptor-mediated synaptic potential evoked in rat medial-amygdala neuron following olfactory bulbectomy." Brain Res.532,No.1. 69-75 (1990)

H.Nakanishi、K.Ukai、T.Nakakawa、S.Watanabe、O.Kamata 和 K.Yamamoto：“嗅球切除术后大鼠内侧杏仁核神经元中 NMDA 受体介导的突触电位的增强。”

Y.Aoki, H.Kimura, T.Hase, T.Shimazu, and M.Naruto: "Low molecular weight peptide inhibitors of medullasin : purification and structure." J.Enzyme Inhibition. 3. 279-287 (1990)

Y.Aoki、H.Kimura、T.Hase、T.Shimazu 和 M.Naruto：“髓质素的低分子量肽抑制剂：纯化和结构。”

Atsushi Ikai: "Electron Microscopic Demonstration of a Common Structural Motif m Human Complement Factor C3 and Rat α_1ーInhibitor 3 (Murinoglobulin)" FEBS Lett.260. 291-293 (1990)

Atsushi Ikai：“人类补体因子 C3 和大鼠 α_1－抑制剂 3（鼠球蛋白）共同结构基序的电子显微镜演示”FEBS Lett.260（1990）。

Kazushi Kunimatsu: "Cathepsin B,H and L Activities in Gingival Crevicular Fluid from Chronic Adult Periodontitis Patients and Experimental Gingivitis Subjects" J.Periodont.Res.25. 69-73 (1990)

Kazushi Kunimatsu：“慢性成人牙周炎患者和实验性牙龈炎受试者龈沟液中的组织蛋白酶 B、H 和 L 活性”J.Periodont.Res.25。