Kenny D, Coughlan M G, Pagel P S, Kampine J P, Warltier D C
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Am Heart J. 1994 Jun;127(6):1456-61. doi: 10.1016/0002-8703(94)90370-0.
The objective of this investigation was to determine the effect of transforming growth factor beta 1 (TGF-beta 1) on endothelium-dependent relaxation in isolated epicardial coronary artery rings obtained from anesthetized dogs after multiple brief episodes of coronary artery occlusion and reperfusion in vivo. Dogs were subjected to four 5-minute periods of left anterior descending coronary artery occlusion interspersed with 5 minutes of reperfusion and followed by a final 1-hour period of reperfusion. Normal left circumflex coronary arteries were used as control samples. Repetitive ischemia and reperfusion significantly (p < 0.01) inhibited the relaxation response to acetylcholine in rings preconstricted with potassium. In an additional group of dogs subjected to the same protocol, 10 micrograms of human recombinant TGF-beta 1 was infused into the left anterior descending coronary artery distal to the site of occlusion via a diagonal branch at 0.3 ml/min immediately before and during the repetitive occlusions and reperfusions. TGF-beta 1 prevented impaired endothelium-dependent relaxation after multiple brief occlusions and reperfusions. These results demonstrate a protective role for TGF-beta 1 in the endothelial injury that occurs during repeated episodes of coronary artery occlusion and reperfusion.
本研究的目的是确定转化生长因子β1（TGF-β1）对在体经历多次短暂冠状动脉闭塞和再灌注后从麻醉犬分离得到的离体心外膜冠状动脉环中内皮依赖性舒张的影响。犬接受4次5分钟的左前降支冠状动脉闭塞，期间穿插5分钟的再灌注，随后进行最后1小时的再灌注。正常左旋冠状动脉用作对照样本。重复性缺血和再灌注显著（p<0.01）抑制了用钾预收缩的冠状动脉环对乙酰胆碱的舒张反应。在另一组接受相同方案的犬中，在重复性闭塞和再灌注之前及期间，通过对角支以0.3 ml/min的速度将10微克人重组TGF-β1注入闭塞部位远端的左前降支冠状动脉。TGF-β1可防止多次短暂闭塞和再灌注后内皮依赖性舒张功能受损。这些结果表明TGF-β1在冠状动脉反复闭塞和再灌注期间发生的内皮损伤中具有保护作用。
