Mechanisms of increased vascular permeability associated with sympathetic excitability and the development of treatment strategy of ARDS.

血管通透性增加与交感神经兴奋相关的机制及ARDS治疗策略的制定。

• 批准号: 16390448
• 负责人: SHIMADA Yasuhiro
• 金额: $ 7.94万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390448/
• 关键词: ARDS; neurogenic pulmonary edema; vascular permeability; vascular regeneration; vascular endothelial cell proliferation; neuropeptide Y; NPYY_3 receptor; Abelson tyrosine kinase; NPY Ya-受容体; Abelson tyrosine kinase; ニューロペプタイドY; 大動脈内皮細胞; 低酸素暴露

Diseases such as adult respiratory distress syndrome (ARDS) have increased pulmonary vascular permeability in its entity and treatment strategy is fundamental importance. We have previously reported in the neurogenic pulmonary edema rats that a substance (neuropeptide y: NPY) coexisting with norepinephrine in the sympathetic nerves exerts vascular permeability. We have further elucidated the relationship between NPY and vascular permeability in the present research.1) Abelson tyrosine kinase (Abl) and vascular permeabilityAbl is one of the protein phosphorylation enzymes related with actin polymerization and intranuclear protein synthesis (transcription factor). Non-specific inhibitors of Abl decreased vascular permeability caused by NPY.2) NPY and cell proliferationIt has been reported that vascular endothelial cell proliferation is closely related with vascular permeability. We have shown that in high NPY, hypoxia increased cell proliferation, whereas normal oxygen concentration caused no proliferation. In low NPY, neither hypoxia nor normal oxygen concentration caused proliferation. As in increased vascular permeability, NPY increased vascular cell proliferation by activation of phospholipase C through protein G and activations of protein kinase C and calmodulin-dependent phosphrylation enzyme.3) Cloning of NPY Y_3 receptorWe have found that the increased proliferation of vascular endothelial cells in hypoxia in the presence of NPY was through NPY Y_3 receptor as was found in increased vascular permeability. However, NPY Y_3 receptor is the only subtype of NPY which has unknown amino acids arrangement. In the NPY Y3 receptor, there would be a chance of transformation of the NPY Y_2 receptor.

成人呼吸窘迫综合征（ARDS）等疾病的实质是肺血管通透性增高，治疗策略至关重要。我们之前报道过在神经源性肺水肿大鼠中，一种与去甲肾上腺素共存的物质（神经肽y: NPY）在交感神经中发挥血管通透性。我们在本研究中进一步阐明了NPY与血管通透性的关系。1) Abelson酪氨酸激酶（Abl）和血管通透性Abl是与肌动蛋白聚合和核内蛋白合成（转录因子）相关的蛋白质磷酸化酶之一。非特异性Abl抑制剂降低NPY引起的血管通透性2)NPY与细胞增殖有报道称血管内皮细胞增殖与血管通透性密切相关。我们已经证明，在高NPY下，缺氧促进细胞增殖，而正常氧浓度则不引起细胞增殖。低NPY时，缺氧和正常氧浓度均不引起增殖。与增加血管通透性一样，NPY通过蛋白G激活磷脂酶C，并激活蛋白激酶C和钙调素依赖性磷酸化酶，从而增加血管细胞的增殖。3) NPY Y_3受体的克隆我们发现NPY存在时，缺氧条件下血管内皮细胞增殖的增加是通过NPY Y_3受体实现的，正如血管通透性的增加一样。然而，NPY Y_3受体是NPY唯一的氨基酸排列未知的亚型。在NPY Y3受体中，NPY Y_2受体也有转化的机会。

项目成果

Protective effects of sarpogrelate, a 5-HT2A antagonist, against postischemic myocardial dysfunction in guinea pig hearts.

沙格雷酯（5-HT2A 拮抗剂）对豚鼠心脏缺血后心肌功能障碍的保护作用。

• 发表时间: 2005
• 期刊: Molecular and Cellular Biochemistry 272
• 作者: Mori K;Yokoyama A;Yang L;Maeda N;Mitsda N;Tanaka J;Tetsuya Muto
• 通讯作者: Tetsuya Muto

Opposing effects of isoflurane and sevoflurane on neurogenic pulmonary edema development in an animal model

• DOI: 10.1097/00000542-200506000-00018
• 发表时间: 2005-06-01
• 期刊: ANESTHESIOLOGY
• 影响因子: 8.8
• 作者: Kandatsu, N;Nan, YS;Ishikawa, N
• 通讯作者: Ishikawa, N

A role of anti-verotoxin antibody immunoreactive peptide, Virp5, from rat spinal cord

大鼠脊髓抗维罗毒素抗体免疫反应肽 Virp5 的作用

• 发表时间: 2004
• 期刊: Peptides 25
• 作者: Asheuer;M.;Pflumo;F.;Benhamida;S.;Dubart-Kupperschmitt;A.;Imai;Y.;Aubourg;P.;Cartier;N.Kupperschmitt;A.;Imai,Y.;Ishikawa Naohisa
• 通讯作者: Ishikawa Naohisa

シンプル薬理学第3版

简单药理学第三版

• 发表时间: 2004
• 作者: Y.Meng;H.Takahashi;J.Meng;Y Zhang;G.Lu;A.Asrar;T.Nakamura;石川直久
• 通讯作者: 石川直久