Roles of lipid mediators in the mechanism of dental pulp tissue injury induced by administration of pharmacological agents

脂质介质在药物致牙髓组织损伤机制中的作用

• 批准号: 02670825
• 负责人: HIRAFUJI Masahiko
• 金额: $ 1.41万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670825/
• 关键词: Dental Pulp; Arachidonate Metabolism; Platelet-activating Factor; Endotoxin; Tissue Injury; Microcirculation Disturbance; Cell-cell Interaction

Endotoxin administration to the rat induces various pathophysiological reactions including changes in PAF(platelet-activating factor)and arachidonate metabolisms in different tissues. We investigated the effect of endotoxin administered systemically on prostagiandin(PG)l_2 and thromboxane(TX)A_2 production in dental pulp tissue in the rat. Intravenous administration of endotoxin induced an increase in both PGl_2 and TXA_2 production in a dose- and time-dependent manner. This effect of endotoxin was not prevented by the pretreatment of PAF antagonist, and was not accompanied by the increase of PAF content in the pulp tissue. Endotoxin had no direct effect on PG and TX production when incubated in vitro with isolated pulp tissues. On the other hand, endotoxin treatment caused an increase only in TXA_2 production by the lung tissue, and had no effect in the intestinal tissue, suggesting that arachidonate metabolism in the pulp tissue is more susceptible to endotoxic shock than in these ti … More ssues. Despite the increase in PG and TX production, endotoxin injection did not cause an increase in vascular permeability in the pulp tissue. However, interestingly, preliminary experiment showed that endotoxin caused a disturbance of dentin formation. The precise mechanisms of effects of endotoxin administration on pulpal arachidonate metabolism and dentin formation remain to be clarified. We also investigated the role of PAF in cell-cell interaction among leukocytes, platelets and endothelial cells, and revealed that PAF induced platelet adhesion to endothelial cell surface when leukocytes were coincubated in vitro, suggesting that such an interaction may play an important role in pathogeheisis of microcirculation disturbance. Thus, the present study indicates that arachidonate metabolism in the pulp tissue can be altered by systematically administered agent, and suggests that this is an useful model for studying the role of arachidonate metagolitbs in pathophysioldgy of the dental pulp injury. Less

内毒素给药大鼠诱导各种病理生理反应，包括血小板活化因子（PAF）和花生四烯酸代谢在不同组织中的变化。本文观察了内毒素对大鼠牙髓组织中前列腺素（PG）_2和血栓素（TX）A_2产生的影响。静脉注射内毒素可引起PGI_2和TXA_2的增加，并呈剂量和时间依赖性。PAF拮抗剂预处理不能阻止内毒素的这种作用，也不伴有牙髓组织中PAF含量的增加。内毒素没有直接影响PG和TX生产时，在体外培养与离体牙髓组织。另一方面，内毒素处理仅引起肺组织TXA_2的产生增加，而对肠组织没有影响，这表明牙髓组织中的花生四烯酸代谢比这些组织中的花生四烯酸代谢更容易受到内毒素休克的影响。 ...更多信息 sweetie。尽管PG和TX的生产增加，内毒素注射并没有引起牙髓组织中的血管通透性增加。然而，有趣的是，初步的实验表明，内毒素引起牙本质形成的障碍。内毒素对牙髓花生四烯酸代谢和牙本质形成影响的确切机制仍有待阐明。我们还研究了PAF在白细胞、血小板和内皮细胞之间的细胞-细胞相互作用中的作用，发现PAF在体外白细胞共孵育时诱导血小板粘附于内皮细胞表面，提示这种相互作用可能在微循环障碍的病理过程中起重要作用。因此，本研究表明，花生四烯酸在牙髓组织中的代谢可以改变系统管理代理，并建议这是一个有用的模型，用于研究的作用花生四烯酸metagolitbs在牙髓损伤的病理生理。少

项目成果

Hirafuji, M. and Shinoda, H.: "Critical role of oxygen-derived free radicals in leukocyte-induced platelet adhesion to endothelial cells in vitro."

Hirafuji, M. 和 Shinoda, H.：“氧自由基在体外白细胞诱导的血小板与内皮细胞粘附中的关键作用。”

Hirafuji, M. and Shinoda, H.: "PAF-mediated platelet adhesion to endothelial cells induced by FMLP-stimulated leukocytes." J. Lipid Mediat.4. 347-352 (1991)

Hirafuji, M. 和 Shinoda, H.：“PAF 介导的血小板与 FMLP 刺激的白细胞诱导的内皮细胞粘附。”

Masahiko Hirafuji: "Critical role of oxygenーderived free radicals in leukocyteーinduced platelet adhesion to endothelial cells in vitro"

Masahiko Hirafuji：“氧源自由基在白细胞板诱导小细胞体外粘附到内皮细胞中的关键作用”

Masahiko Hirafuji: "Distinct stimulatory effect of platelet-activating factor on prostaglandin I_2 and thromboxane A_2 bionsynthesis by rat dental pulp" Europ. J. Pharmacol.185. 81-90 (1990)

Masahiko Hirafuji：“血小板活化因子对大鼠牙髓前列腺素 I_2 和血栓素 A_2 生物合成的明显刺激作用”Europ。

Masahiko Hirafuji: "Distinct stimulatory effect of plateletーactivating factor on prostaglandin I_2 and thromboxane A_2 biosynthesis by rat dental pulp" Europ.J.Pharmacol.185. 81-90 (1990)

Masahiko Hirafuji：“血小板活化因子对大鼠牙髓前列腺素 I_2 和血栓素 A_2 生物合成的明显刺激作用”Europ.J.Pharmacol.185 (1990)。