A new strategy of the regulation of metabolic syndrome and cardiovascular diseases by the pharmacological targeting of cellular mechanical stress reactions.

通过细胞机械应激反应的药理学靶向调节代谢综合征和心血管疾病的新策略。

• 批准号: 22616007
• 负责人: TANABE Yoshiyuki
• 金额: $ 2.91万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22616007/
• 关键词: メカニカルストレス; メタボリックシンドローム; 脂肪細胞; マクロファージ; PPAR-γ; サイトカイン; 肺高血圧; ホスホリパーゼA2; 脂肪組織; シクロオキシゲナーゼ; sPLA2; アディポサイトカイン; 肺高血圧症; アポトーシス

The effects of abdominal vibration were examined using obese mice with high-fat diet. Daily exposure of the 30-minutes-vibration induced downregulation of adipogenic factors and upregulation of anti-adipogenic factor, which consisted with decreasing adipose tissue triglyceride, some adipokines, and plasma free fatty acids. Furthermore, augmented expressions of several genes characteristic of anti-inflammatory M2 macrophages (Mφ) were detected. The effects of selective sPLA2 inhibitor (indoxam) on the pathogenicity of MCT-induced fatal pulmonary hypertensive rats (MCT-PHR) were also examined. Indoxam abolished the enhanced contractilities of the pulmonary arteries of MCT-PHR, which arteries show augmented expression of sPLA2-X isoform. In addition, administration of indoxam attenuated some inflammatory signs such as expression of proinflammatory cytokines and apoptosis in the lung, leading to a significant improvement of survival ratio in MCT-PHR.

用高脂饮食的肥胖小鼠检测腹部振动的影响。每天接触30分钟的振动可导致成脂因子表达下调，抗成脂因子表达上调，表现为脂肪组织甘油三酯、某些脂肪因子和血浆游离脂肪酸水平降低。此外，还检测到抗炎M2巨噬细胞(M-φ)的几个特征基因的表达增强。此外，还观察了选择性sPLA2抑制剂(吲哚青霉素)对MCT致死性肺动脉高压大鼠(MCT-PHR)致病性的影响。Indoxam可抑制MCT-PHR大鼠肺动脉收缩增强，表现为sPLA2-X亚型表达增强。此外，吲哚青能减轻肺组织中促炎症细胞因子的表达和细胞凋亡等炎症征象，显著提高MCT-PHR的存活率。

项目成果

Role of Secretory Phospholipase A<SUB>2</SUB> in Rhythmic Contraction of Pulmonary Arteries of Rats With Monocrotaline-Induced Pulmonary Arterial Hypertension

分泌型磷脂酶A<SUB>2</SUB>在野百合碱所致肺动脉高压大鼠肺动脉节律性收缩中的作用

• DOI: 10.1254/jphs.12024fp
• 发表时间: 2012
• 期刊: Journal of Pharmacological Sciences
• 影响因子: 3.5
• 作者: Tanabe Y;Saito-Tanji M;Morikawa Y;Kamataki A;Sawai T;Nakayama K
• 通讯作者: Nakayama K

バイオメカニカルストレスによる脂肪細胞・組織での細胞分化・代謝機能制御の試み

尝试通过生物力学应力控制脂肪细胞和组织的细胞分化和代谢功能

• 发表时间: 2012
• 作者: 田辺由幸;丹治(斉藤)麻希;鎌滝章央;澤井高志;中山貢一
• 通讯作者: 中山貢一

Mechanosensitivity of pancreatic β-cells, adipocytes, and skeletal muscle cells: the therapeutic targets of metabolic syndrome.

胰腺β细胞、脂肪细胞和骨骼肌细胞的机械敏感性：代谢综合征的治疗靶点。

• DOI: 10.1007/978-94-007-5073-9_14
• 发表时间: 2012
• 期刊: Mechanosensitivity in Cells and Tissues
• 作者: Nakayama K;Tanabe Y;Obara K;Ishikawa T
• 通讯作者: Ishikawa T

分泌型ホスホリパーゼA2阻害薬インドキサムは肺動脈圧の低下無しにモノクロタリン誘発肺高血圧症ラットの生存期間を延長する

分泌型磷脂酶 A2 抑制剂 indoxam 可以延长野百合碱诱导的肺动脉高压大鼠的生存期，而不会降低肺动脉压力。

• 发表时间: 2012
• 作者: 斉藤麻希;田邉由幸;鎌滝章央;澤井高志;菅野美紅;中山貢一.
• 通讯作者: 中山貢一.

Involvement of secretory phospholipase A2 in the rhythmic contraction of pulmonary arteries produced by stretching in monocrotaline-induced pulmonary arterial hypertensive rats and possible implication for the pathogenicity.

分泌型磷脂酶 A2 参与野百合碱诱导的肺动脉高血压大鼠拉伸引起的肺动脉节律性收缩及其致病性的可能意义。

• 发表时间: 2013
• 期刊: Journal of Pharmacological Sciences
• 影响因子: 3.5
• 作者: Saito M;Tanabe Y;Kamataki A;Sawai T;Nakayama K
• 通讯作者: Nakayama K