冬眠誘発因子(D-Ala2-Leu5-enkephalin)の心筋保護への応用

冬眠诱导因子(D-Ala2-Leu5-脑啡肽)在心肌保护中的应用

• 批准号: 11770753
• 负责人: 林田 信彦
• 金额: $ 0.51万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11770753/
• 关键词: 冬眠誘発因子; 心筋保護; 虚血再灌流障害; enkephalin; 心筋代謝; D-Ala2-Leu5-enkephalin

研究実績の概要非虚血心における冬眠誘発因子のD-Ala2-Leu5-enkephalin(DADLE)投与の循環動態及び心筋代謝に及ぼす影響及びnaloxaneによる拮抗作用を検討した。本実験に先立って心筋障害、再灌流障害の指標としてheart fatty acid-binding protein、接着因子(E-selectin,ICAM-1,VCAM-1),ANP,BNP,TBARSが本実験群の比較検討に有用かつ妥当であるか否かを検討し報告した。さらにDADLEは細胞膜のdelta opioid receptorに作用するが、その発現にcAMP及びcGMPが関与することが報告されているがcAMP増加薬剤であるforskolin及びcGMP増加薬剤のHANPの心筋に対する効果も検討し報告した。以上の結果をふまえて以下の研究を行った。[1]実験動物:Wistar系rat20匹を使用した。[2]実験方法:血液交叉体外循環回路に、摘出心を装着し、心筋保護液を心停止を120分間行った。30分間の再潅流後working modeとした。DADLE及びその阻害薬であるnaloxaneの投与の有無及び投与方法により、以下の5群に分類し比較検討した。Control群:通常の心筋保護心停止を行った群DADLE pre群:心筋保護心停止1時間前にDADLEを1mg/kg/hrの速度で1時間全身投与した群DADLE xcl群:心筋保護液にDADLEを2mmol/L添加し投与した群DADLE pre+xcl群:心停止前及び心筋保護液中にDADLEを上記の方法で投与した群Naloxane群:DADLE pre+xcl群に再灌流中naloxaneを3mg/kg/hrで30分間投与した群[3]結果:心機能はDADLE pre+xcl群で温存されており心筋障害、再灌流障害の指標であるheart fatty acid-binding protein、接着因子、TBARSの発現も同群で低値を示した。本研究により虚血心に対するDADLEの心筋保護効果が示唆され、本研究結果を医学雑誌に報告予定である。

The summary of the study was that the hibernating factor D-Ala2-Leu5-enkephalin (DADLE) was used to study the antagonism of hibernating factors (D-Ala2-Leu5-enkephalin) and the antagonism of hibernating factors, such as hibernation and hibernation. In this paper, we first set up the concept of heart disorder and reperfusion injury, which refers to the symptoms of heart fatty acid-binding protein, and then the factors (Eluto selectin, ICAMMB, ICAMMAUL, VCAM, and so on), and the ANP,BNP,TBARS is more useful than others. The effect of the membrane delta opioid receptor on the cell membrane is different. The cAMP and the cGMP are detected. The cAMP is added to the report. The forskolin and the cGMP are added to the HANP. The above results indicate that the following studies will be conducted. [1] Wistar is used as a match for rat20. [2] Therapy method: blood crossover extracorporeal circuit, heart extraction, heart arrest and cardiac arrest for 120 minutes. After 30 minutes, the working mode will be closed again. DADLE and other information systems prevent the development of naloxane and investment methods. The following 5 groups are classified and compared. Control group: general cardioplegia group DADLE pre group: before cardiac arrest 1 hour, whole body 1mg/kg/hr speed 1 time interval DADLE xcl group: cardiomyocardial solution DADLE 2mmol/L addition group DADLE pre+xcl: group DADLE pre+xcl: before cardiac arrest and in cardiomyopathy solution, the method of DADLE uplink injection and cluster Naloxane group: naloxane group in DADLE pre+xcl group reperfusion 3mg/kg/hr 30-minute voting and clustering [3] results: the heart machine can help the DADLE pre+xcl group to warm up and worry about heart disorders, Reperfusion injury refers to the symptoms of heart fatty acid-binding protein, followed by factors, TBARS factors show that the same group of low temperature shows that. The results of this study are based on the results of DADLE heart protection, and the results of this study are based on medical journal reports.

项目成果

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