動脈硬化および末梢血管抵抗増大モデルによる局所心筋機能と左室弛緩機能の分析

利用动脉硬化和外周血管阻力增加模型分析局部心肌功能和左心室舒张功能

• 批准号: 09470540
• 负责人: 久萬田 俊明
• 金额: $ 1.02万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470540/
• 关键词: 左室弛緩機能; 圧負荷; 蛋白合成; カルシウム拮抗薬; 壁厚

【目的】1.左室陽性変力状態下、およびCa拮抗薬投与により上行大動脈(AA)と下行大動脈(DA)の狭窄中の左室弛緩機能(時定数;T)の変化を観察した。2.持続的大動脈狭窄により動脈壁・心筋の蛋白合成の有無を調べた。【方法】6匹の痲酔開胸犬をrespiratorで換気。AAとDAに狭窄用テープを装着。左頚動脈からMillarカテーテルを大動脈弁直上まで挿入し(動脈圧測定)、左心耳からKonigsberg圧力計を左室内に挿入(左室圧測定)。左室心基部に一対の超音波クリスタルを装着(壁厚増加率(%W)の測定)。無投薬時(C群)、プロタノール静注時(P群)、ヘルベッサー静注時(H群)に、AAとDAを急速狭窄した(血圧40mmHg上昇)。別の犬1匹に上記と同一機具を設置、DAを20-30分間狭窄(血圧を30-40mmHg上昇)した後、直ちに心臓と大動脈を摘出。左室心基部、心尖部、大動脈の凍結切片より免疫沈降したp42/p44Extracellular Signal Regulated Protein Kinase(ERK)をATP存在下にEIK1-GST融合蛋白と燐酸化反応を行わせることにより得られたphosphorylated Eik1を特異抗体を用いたimmunoblot法により検出(densitometry法によりERK活性を評価)。【結果】1.AA狭窄では、3群ともに収縮末期大動脈圧(AoESP)は上昇せず、同値(82mmHg)にも拘わらず、H群のTのみ増加。DA狭窄では、AoESPは各群ともに同程度上昇(+△50mmHg)し、C群とH群のTが増加。%WはDA狭窄時のC群とH群のみ有意に減少。2.大動脈、心筋ともにERKの活性化が生じた。【考案】心筋の弛緩にはCa動態が深く関与していること、および機械的圧負荷で大動脈と心筋の蛋白合成が活性化される可能性が示唆された。

[Objective] 1. To observe the changes of left ventricular relaxation function (T) in the stenosis of ascending artery (AA) and descending artery (DA) under the condition of left ventricular positive tension. 2. The presence or absence of regulation of protein synthesis in persistent arterial stenosis [Method] 6 leprosy open-chested dogs were replaced by respirators. AA is narrow. The left atrial appendage (LAA), the left atrial appendage (LAA), and the left ventricular pressure (LVP) were measured by the Konigsberg manometer. A pair of ultrasonic instruments were installed at the base of the left ventricle (measurement of wall thickness increase rate (%W)). No drug (group C), no drug (group P), no drug (group H), no drug (group AA), no drug (group D), no drug (group C), no drug (group P), no drug (group H), no drug (group A), no drug (group B), no drug (group C), no drug (group C), no drug (group D), no drug (group C), no drug (group C), no drug (group P), no drug (group H), no drug (group C), no drug (group D), no drug (group D), no drug (group C), no drug (group D), no drug (group D), no drug (group C), no drug (group D), no drug (group C), no drug (group D), no drug (group D The same machine settings, DA 20-30 minutes narrow (blood pressure 30-40mmHg rise), straight heart and artery extraction Frozen sections of the left ventricular base, apex, and aorta were prepared by immunoblotting p42/p44Extracellular Signal Regulated Protein Kinase(ERK) in the presence of ATP to detect EIK1-GST fusion protein and phosphorylated Eik1 specific antibodies. [Results] 1. AoESP increased in AA stenosis, AoESP increased in group 3, AoESP increased in group H at 82mmHg. DA stenosis and AoESP increased in the same degree (+△50mmHg), and T increased in group C and group H. % When W DA is narrow, C group and H group are intentionally reduced. 2. The activation of ERK in the aorta and heart muscle was observed. The possibility of activation of cardiac muscle protein synthesis due to mechanical stress is also discussed.