Padua R R, Sethi R, Dhalla N S, Kardami E
St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Mol Cell Biochem. 1995 Feb 23;143(2):129-35. doi: 10.1007/BF01816946.
To examine whether basic fibroblast growth factor (bFGF) administered to the heart by perfusion can improve cardiac resistance to injury we employed an isolated rat heart model of ischemia-reperfusion injury and determined the extent of functional recovery in bFGF-treated and control hearts. Global ischemia was simulated by interruption of flow for 60 min. Recovery of developed force of contraction (DF), recorded after reestablishment of flow for 30 min, reached 63.8 +/- 1.5% and 96.5 +/- 3.5% of preischemic levels in control and bFGF-treated hearts (10 micrograms/heart), respectively, indicating that bFGF induced significantly improved recovery of mechanical function. Recoveries of the rates of contraction or relaxation were also significantly improved in bFGF-treated hearts. Extent of myocardial injury, assessed by determination of phosphocreatine kinase in the effluent, was reduced as a result of bFGF treatment. As a first step towards understanding the mechanism and direct cellular target(s) of bFGF-induced cardioprotection, we investigated its fate after perfusion. Perfusion of 10 micrograms bFGF/heart resulted in a 4-fold increase in bFGF associated with the heart compared to control levels, as estimated by biochemical fractionation and immunoblotting. Immunofluorescent staining of the bFGF-perfused hearts revealed intense anti-bFGF staining in association with blood vessels as well as the periphery of cardiomyocytes, suggesting that the latter may be a target for direct bFGF action. In conclusion, our findings of bFGF-induced increases in cardiac resistance to, and improved functional recovery from, ischemia-reperfusion injury indicate that bFGF may have clinical applications in the treatment of ischemic heart disease.
为了研究通过灌注给予心脏碱性成纤维细胞生长因子（bFGF）是否能提高心脏对损伤的耐受性，我们采用了离体大鼠心脏缺血再灌注损伤模型，并测定了bFGF处理组和对照组心脏的功能恢复程度。通过阻断血流60分钟模拟全心缺血。再灌注30分钟后记录的收缩峰力（DF）恢复情况，对照组和bFGF处理组心脏（10微克/心脏）分别达到缺血前水平的63.8±1.5%和96.5±3.5%，表明bFGF能显著改善机械功能的恢复。bFGF处理组心脏的收缩或舒张速率恢复也显著改善。通过测定流出液中磷酸肌酸激酶来评估心肌损伤程度，结果显示bFGF处理可减轻心肌损伤。作为了解bFGF诱导心脏保护机制和直接细胞靶点的第一步，我们研究了灌注后bFGF的去向。通过生化分级分离和免疫印迹估计，每心脏灌注10微克bFGF导致与心脏相关的bFGF比对照水平增加了4倍。对bFGF灌注心脏进行免疫荧光染色显示，与血管以及心肌细胞周边相关的抗bFGF染色强烈，提示心肌细胞周边可能是bFGF直接作用的靶点。总之，我们发现bFGF可增加心脏对缺血再灌注损伤的耐受性并改善功能恢复，这表明bFGF在缺血性心脏病治疗中可能具有临床应用价值。
