Molecular-Pharmacological Analysis of Periodontal Disease : Interaction between LPS and Kinins on Microcirculation of Oral Region

牙周病的分子药理学分析：脂多糖和激肽对口腔微循环的相互作用

• 批准号: 03670879
• 负责人: TODOKI Kazuo
• 金额: $ 1.28万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670879/
• 关键词: Periodontal disease; Endotoxin; bradykinin; Lingual artery; Endothelium; nitric oxide; Oxygen free radicals; Prostanoide; 血管平滑筋; 内皮由来弛緩因子(EDRF); 電子スピン共鳴法; エンドトキシン; 内皮細胞由来弛緩因子; 収縮; B_<1->受容体; B_<2->受容体

In this research project, we wished to determine 1) the effect of bradykinin on lingual artery ; 2) the interaction between LPS and bradykinin on lingual artery and 3) the effect of LPS on transmural nerve stimulation-induced contraction of the isolated mesenteric artery. Oxygen free radical participation in the effect of LPS was investigated. The following results were obtained : 1. Bradykinin-induced contraction may be mediated by an increase of intracellular free Ca ion by B_2 receptors-coupled phosphoinositide (PI) turnover in canine vascular smooth muscle, and bradykinin-induced relaxation may be mediated by a liberated vasodilator substance (e.g.nitric oxide) by the stimulation of the endothelial B_2 receptors, which possibly activates guanylate cyclase to accumulate cGMP in smooth muscle. 2. LPS induces the formation of B_1-kinin receptor in rabbits. The activation of B_1-kinin receptors by des-Arg^9-bradykinin produces contraction of the lingual arteries isolated from the rabbi … More t intravenously treated with LPS.3.LPS inhibits the release of norepinephrine from sympathetic nerve endings by stimulating both prejunctional inhibitory muscarinic- and alpha_2-adrenoceptors. The effect of LPS may involved protein synthesis. 4. LPS by itself can generate oxygen free radicals ( OH radical) via superoxide-dependent and/or Fenton and Harber-Weiss reactions. 5. OH radical selectively damage endothelium-dependent relaxation. It is also postulated that lipid peroxidation may be responsible for this effect.Finally, it is likely that a sequential activation or/and a modulatory activity of bradykinin, kinin analogous, prostaglandins, and oxygen free radicals via the LPS-interaction is involved in the progression of periodontal disease. Furthermore, one must now begin to put the functional receptor de novo formation hypothesis of the effect of LPS on vascular reactivity in perspective. A through understanding of the endogenous regulatory mechanisms of hemodynamics in oral tissues may be of interest for the development of new concepts of treatment in dental therapeutics in the future. Less

在本研究中，我们希望确定1)缓激肽对舌动脉的作用；2)脂多糖和缓激肽对舌动脉的相互作用；3)脂多糖对神经刺激引起的离体肠系膜动脉收缩的影响。探讨氧自由基在内毒素作用中的作用。结果如下：1.缓激肽引起的收缩可能是通过B_2受体偶联的磷脂酰肌醇(PI)引起的犬血管平滑肌细胞内游离钙离子周转增加，而缓激肽引起的收缩可能是通过刺激内皮B_2受体释放出的血管扩张物质(如一氧化氮)，激活鸟苷环化酶，使cGMP积聚在血管平滑肌中而实现的。2.脂多糖可诱导兔β_1-激肽受体的形成。DES-Arg^9-Bradykinin激活B_1-激动素受体引起…拉比分离的舌动脉收缩静脉注射更多的LPS。3.通过刺激交感神经末梢交感前抑制性M受体和α_2受体，可抑制交感神经末梢释放去甲肾上腺素。内毒素的作用可能与蛋白质合成有关。4.脂多糖本身可以通过超氧化物依赖和/或Fenton反应和Harber-Weiss反应产生氧自由基(OH自由基)。5.羟基自由基选择性损伤内皮依赖性松弛。最后，可能是缓激肽、激肽类似物、前列腺素和氧自由基通过脂多糖相互作用的顺序激活或/和调节活性参与了牙周病的进展。此外，人们现在必须开始正确看待内毒素对血管反应性的影响的功能性受体从头形成假说。通过了解口腔组织血流动力学的内源性调节机制，可能会对未来牙科治疗学中新的治疗概念的发展感兴趣。较少

项目成果

杉原 昌実: "Endotoxinによって生ずるB_1-受容体を介した摘出ウサギ舌動脈の収縮反応." 日薬理誌. 98(2). 63-71 (1991)

Masami Sugihara：“内毒素诱导的 B_1 受体介导的离体兔舌动脉收缩反应。”98(2) (1991)。

Shijezi Tomikawa: "Endotoxin impairs the responce of rabbit mesenteric artery to electrical stimulation via a prejunctional mechanism." Br.J.Pharmacol.107(3). 826-832 (1992)

Shijezi Tomikawa：“内毒素通过预连接机制损害兔肠系膜动脉对电刺激的反应。”

Masami Sugihara: "The contractile response of isolated lingual arteries from rabbits treated with bacterial lipopolysaccharide via the stimulation of B_1-receptors for kinins" Folia pharmacol. Japon.98(2). 63-71 (1991)

Masami Sugihara：“通过刺激激肽 B_1 受体，用细菌脂多糖处理兔子的离体舌动脉的收缩反应”Foliapharmacol。

Sigeji Tomikawa: "The inhibition of electrical stimulationーinduced vasocontraction by E.coli endotoxin" Microcirc.ann.25-26 (1990)

Sigeji Tomikawa：“大肠杆菌内毒素对电刺激诱导的血管收缩的抑制”Microcirc.ann.25-26 (1990)

Kazuo Todoki: "Proceeding,Oxygen Radicals" Elsevier Science Publishers B.V., (1992)

Kazuo Todoki：“氧自由基进展”Elsevier Science Publishers B.V.，（1992 年）