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Inhibition of Degranulation of Resident Cardiac Mast Cells May Prevent Ischaemia and Reperfusion-induced Myocardial injury

机译:抑制常规心脏肥大细胞脱粒可能预防缺血性和再灌注诱导的心肌损伤

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Summary. The present study is designed to investigate the role of resident cardiac mast cells in ischaemia and reperfusion-induced apoptotic and necrotic death of cardiomyocytes. Isolated perfused rat heart was subjected to 30min of global ischaemia followed by reperfusion for 120 min. The extent of mast cell degranulation was determined by the release of mast cell peroxidase (MPO) in the coronary effluent. Release of LDH, CK in the coronary effluent and estimation of infarct size are employed to assess the extent of myocardial injury. DNA fragmentation analysis using terminal deoxynudeotidyl transferese-mediated UTP nick end-labeling (TUNEL) and agarose gel electrophoresis are employed to estimate apoptotic death of cardiomyocytes. Disodium cromoglycate (DSCG, 100 uM), theophylline (100 uM) and FR 167653 (2.2uM) treatment before global ischaemia and reperfusion are noted to reduce degranulation of resident cardiac mast cells, measured in terms of MPO release and has produced cardioprotective effect assessed as infarct size and release of LDH and CK. DSCG, theophylline and FR 167653 treatment has also markedly reduced the number of TUNEL positive cardiomyocytes and ventricular DNA smearing. These results tentatively suggest that DSCG, theophylline and FR 167653 inhibit degranulation of resident cardiac mast cells and consequently prevent ischaemia and reperfusion induced apoptosis and apoptosis induced necrosis in cardiomyocytes.
机译:概括。本研究旨在探讨常驻心脏肥大细胞在患有缺血性和再灌注诱导的心肌细胞的细胞凋亡和坏死性死亡中的作用。将分离的灌注大鼠心脏进行30分钟的全球性血症,然后再灌注120分钟。通过在冠状动脉流出物中释放肥大细胞过氧化物酶(MPO)来确定桅杆细胞脱粒的程度。释放LDH,CK在冠状动脉污水中,采用梗死大小的估计来评估心肌损伤的程度。使用末端脱辛稳平阳酰转移介导的UTP缺口末端标记(TUNEL)和琼脂糖凝胶电泳的DNA碎片分析用于估计心肌细胞的凋亡死亡。冠状甘露糖(DSCG,100μm),茶碱(100μm)和FR 167653(2.2um)治疗在全球性缺血和再灌注之前治疗,以减少常规心脏肥大细胞的升级,以MPO释放为单位测量,并产生了对心脏保护作用进行评估作为LDH和CK的梗塞大小和释放。 DSCG,Theophylline和FR 167653治疗也显着降低了Tunel阳性心肌细胞和心室DNA涂抹的数量。这些结果暂定表明,DSCG,Theophylline和Fr 167653抑制了常规心脏肥大细胞的缩减,从而预防缺血和再灌注诱导的凋亡和细胞凋亡诱导心肌细胞的坏死。

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