Prevention of coronary vascular abnormalities early in reperfusion with TGF-beta may not prevent late coronary vascular injury.
Prevention of coronary vascular abnormalities early in reperfusion with TGF-beta may not prevent late coronary vascular injury.
复制标题
在再灌注早期用 TGF-β 预防冠状血管异常可能无法预防晚期冠状血管损伤。
DOI：
10.1097/00005344-199708000-00008
复制
发表时间：
1997
影响因子：
3
通讯作者：
Horwitz,L
中科院分区：
文献类型：
--
作者：
Keller,M;Kong,Y;Robertson,AD;Horwitz,L
在缺血后的再灌注过程中，内皮损伤表现为蛋白质渗漏增加和内皮依赖性舒张功能降低。转化生长因子-β（TGF-β）已被证明可以改善内皮依赖性舒张，并在短期（20 min至4.5 h）再灌注后缩小梗死面积，即使在缺血期前24 h给药。然而，这是否代表导致内皮损伤或预防损伤的过程中的短暂延迟尚不清楚。为了研究这个问题，我们测量了缺血前30分钟用TGF-β（30 μg/kg，iv）治疗的狗和对照狗在短暂（1小时）和漫长（48小时）再灌注期后的蛋白质渗漏（冠状动脉微血管通透性的指标）和内皮依赖性舒张（冠状动脉内皮功能的指标）。结扎冠状动脉左前降支（LAD）1h后再灌注1h（n= 10）或再灌注48 h（n= 12）。通过放射性标记的转铁蛋白和红细胞，通过双同位素技术评估蛋白质渗漏，并通过使用二磷酸腺苷（ADP）（内皮依赖性血管扩张剂）和硝普钠（SNP）（内皮非依赖性扩张剂）评估心外膜冠状动脉环的内皮依赖性舒张。在对照动物中，与非缺血心肌（1 h时为3.1±0.8，48 h时为3.8±0.9）相比，梗死区的蛋白渗漏指数（PLI）显著增加（1 h时为8.3±1.4，48 h时为8.7 ± 0.9）。在TGF-β治疗的狗中，在1小时的狗中梗死区的PLI有显著改善（PLI，4.1±1.1; p< 0.05;或与未治疗的狗相比降低50%）。然而，用TGF-β处理48小时的狗未能证明PLI的改善（PLI，8.5±0.9; p= NS）。对照犬LAD内皮依赖性舒张功能受损，再灌注1或48 h后TGF-β治疗未能改善舒张功能。在缺血再灌注1和48 h后，微血管通透性增加，内皮依赖性舒张功能下降。TGF-β预处理可降低再灌注1h的通透性增加，但对48 h的通透性增加无影响。
Endothelial injury, manifest by increased protein leak and decreased endothelium-dependent relaxation, occurs during reperfusion after ischemia. Transforming growth factor-β (TGF-β) has been shown to improve endothelium-dependent relaxation and reduce infarct size after short periods (from 20 min to 4.5 h) of reperfusion even when administered 24 h before the ischemic period. However, whether this represents a transient delay in the process leading to endothelial injury or prevention of injury has not been clear. To examine this issue, we measured protein leak, an index of coronary microvascular permeability, and endothelium-dependent relaxation, a measure of coronary endothelial function, after brief (1-h) and lengthy (48-h) reperfusion periods in dogs treated 30 min before ischemia with TGF-β (30 μg/kg, iv) and control dogs. The left anterior descending coronary artery (LAD) was ligated for 1 h followed by 1 h of reperfusion (n= 10) or 48 h of reperfusion (n= 12). Protein leak was assessed by a dual-isotope technique by using radiolabeled transferrin and erythrocytes, and endothelium-dependent relaxation was assessed in epicardial coronary rings by using adenosine diphosphate (ADP), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent dilator. In control animals, there was a marked increase in the protein leak index (PLI) in the infarct zone (8.3±1.4 in 1-h dogs, and 8.7±0.9 in 48-h dogs) compared with the nonischemic myocardium (3.1±0.8 at 1 h, and 3.8±0.9 at 48 h). In TGF-β treated dogs, there was a marked improvement in PLI in the infarct zone in 1-h dogs (PLI, 4.1±1.1; p< 0.05; or a 50% reduction compared with untreated dogs). However, the 48-h dogs treated with TGF-β failed to demonstrate an improvement in PLI (PLI, 8.5±0.9; p= NS). Endothelium-dependent relaxation was impaired in the LAD in control dogs, and treatment with TGF-β failed to improve relaxation after 1 or 48 h of reperfusion. Microvascular permeability was increased and endothelium-dependent relaxation was decreased after ischemia at both 1 and 48 h of reperfusion. Pretreatment with TGF-β reduced the increase in permeability at 1 h of reperfusion but not at 48 h.