CAJ | 학술논문

目的利用Langendorff离体灌注模型探讨Ro-54864对缺血/再灌注心肌功能和线粒体的保护作用.方法大鼠心脏上架平衡20min后,随机分为5组.假手术组:持续灌注115min;对照组:续灌10min,缺血25min,复灌60min;Ro(Ro-54864)组:缺血前灌注含0.1μmol/L Ro-54864的K-H液10 min;苍术苷(atractyloside,ATR)组:缺血前灌注含20 μmol/L苍术苷的K-H液10 min;ATR+Ro组:缺血前灌注含20 μmol/L苍术苷和0.1 μmol/L Ro-54864的K-H液10 min.分别在平衡20min、缺血前、复灌15 min、60 min记录左室力学指标.在复灌注末,用氯化三苯基四氮唑染色法(TTC)测定心肌梗死面积百分比;分离浆膜下线粒体,电镜下观察线粒体的形态和结构,并进行评分.结果再灌注15 min后,Ro组的冠脉流量(CF)和血流动力学指标(LVDP,dp/dtmax,dp/dtmin)明显高于对照组和其它处理组,而ATR组的各指标低于对照组(P＜0.05).与对照组(41%±3%)比较,再灌注末期Ro组(28%±3%)心肌梗死面积明显减少(P＜0.05),而ATR组(51%±2%)的梗死面积明显增大(P＜0.05).Ro组(1.51±0.24)心肌线粒体损伤比对照组(2.21±0.27)明显减轻(P＜0.05),而ATR组(3.23±0.36)线粒体损伤较对照组严重(P＜0.05).ATR+Ro组的各项指标与对照组比较无统计学差异.结论外周苯二氯(卓)受体(peripheral benzodi azepine receptor,PBR)激动剂Ro-54864能够明显减少缺血心肌的梗死面积,保护线粒体,增加冠脉流量,促进缺血心肌功能恢复.线粒体通透性转换孔开放剂苍术苷减弱Ro-54864的心肌保护作用.
목적 이용Langendorff리체관주모형탐토Ro-54864대결혈/재관주심기공능화선립체적보호작용.방법 대서심장상가평형20min후,수궤분위5조.가수술조:지속관주115min;대조조:속관10min,결혈25min,복관60min;Ro(Ro-54864)조:결혈전관주함0.1μmol/L Ro-54864적K-H액10 min;창술감(atractyloside,ATR)조:결혈전관주함20 μmol/L창술감적K-H액10 min;ATR+Ro조:결혈전관주함20 μmol/L창술감화0.1 μmol/L Ro-54864적K-H액10 min.분별재평형20min、결혈전、복관15 min、60 min기록좌실역학지표.재복관주말,용록화삼분기사담서염색법(TTC)측정심기경사면적백분비;분리장막하선립체,전경하관찰선립체적형태화결구,병진행평분.결과 재관주15 min후,Ro조적관맥류량(CF)화혈류동역학지표(LVDP,dp/dtmax,dp/dtmin)명현고우대조조화기타처리조,이ATR조적각지표저우대조조(P＜0.05).여대조조(41%±3%)비교,재관주말기Ro조(28%±3%)심기경사면적명현감소(P＜0.05),이ATR조(51%±2%)적경사면적명현증대(P＜0.05).Ro조(1.51±0.24)심기선립체손상비대조조(2.21±0.27)명현감경(P＜0.05),이ATR조(3.23±0.36)선립체손상교대조조엄중(P＜0.05).ATR+Ro조적각항지표여대조조비교무통계학차이.결론 외주분이록(탁)수체(peripheral benzodi azepine receptor,PBR)격동제Ro-54864능구명현감소결혈심기적경사면적,보호선립체,증가관맥류량,촉진결혈심기공능회복.선립체통투성전환공개방제창술감감약Ro-54864적심기보호작용.
Objective To investigate the protective effect of Ro -54864 on ischemia reperfusion myocardial function and mitochondrial in the isolated perfused Langendorff model. Methods After equilibration for 20 min, the hearts were randomly allocated into 5 groups as follows. Sham group: perfusion for 115 min in a Krebs-Henseleit (K-H) buffer. Control group: global ischemia for 25 min followed by reperfusion for 90 min. Ro group: administration of 0.1 μmol/L Ro-54864 K-H buffer for 10 min before ischemia; ATR group: administration of 20 μmol/L atractyloside K-H buffer for 10 min before ischemia; ATR+Ro group: administration of 0.1 μmol/L Ro-54864 and 20 μmol/L atractyloside K-H buffer for 10 min before ischemia. Separate experiments were performed to determine homodynamic variables after equilibration for 20 min, before ischemia, after reperfusion for 15 min, and 60 min. At the end of reperfusion, infarct size was determined with 2,3, 5-triphenyltetrazolium chloride(TTC) staining. And the subsarcolemmal mitochondria (SSM) was isolated and its morphology was observed and quantified under the electron microscope. Results After reperfusion for 15 min and 60 min, homodynamic variables and CF in Ro group were higher than the other groups, Ro-54864 decreased infarct size significantly (28%±3% vs. 41%±3% in control hearts; P＜0.05), and myocardial mitochondrial damage in Ro Group reduced significantly than that of the control group. However, the outcome of ATR group were adverse, and those parameters in ATR+Ro group were equivalent with respect to the Control group. Conclusion The peripheral benzodiazepine receptor, Ro -54864, salvages myocardium from infarction and protectes ischemic heart mitochondria and improves functional recovery. Nonetheless, the mitochondrial permeability transition pore opener, atractyloside, deteriorated ischemic myocardial injury, reduce the protective effect of Ro54864 on ischemic myocardial.