Ayhan Sühan, Tugay Cemil, Norton Steven, Araneo Barbara, Siemionow Maria
Department of Plastic and Reconstructive Surgery, The Cleveland Clinic Foundation, Ohio, 44195, USA.
Plast Reconstr Surg. 2003 Jun;111(7):2286-94. doi: 10.1097/01.PRS.0000060242.85268.8F.
Adhesion molecules contribute to ischemia-reperfusion injury by increasing the endothelial adhesion and extravasation of leukocytes. Scientific evidence suggests that presurgical treatment with dehydroepiandrosterone may protect the microvasculature against this damage, but the exact mechanism is not known. The purpose of this study was to investigate the effects of presurgical dehydroepiandrosterone treatment on microcirculatory hemodynamic parameters and the expression of adhesion molecules in a rat cremaster muscle flap model. Twenty male rats were randomly assigned to three experimental groups. In group I (n = 5), the muscle flaps did not receive presurgical treatment. In group II (n = 6), propylene glycol (30 mg/kg), the vehicle for dehydroepiandrosterone, was injected intravenously before ischemia was induced. In group III (n = 9), dehydroepiandrosterone (30 mg/kg) was injected intravenously before ischemia was induced. All flaps were subjected to 6 hours of ischemia and 90 minutes of reperfusion. Microcirculatory variables (functional capillary density, red blood cell velocity in the main flap arteriole, and numbers of rolling, sticking, and transmigrating leukocytes), blood levels of three adhesion molecules (L-selectin, Mac-1 integrin, and CD44), and the numbers of leukocytes expressing those molecules were analyzed. Analysis of the microcirculatory parameters revealed that dehydroepiandrosterone treatment before ischemia had significant preservative effects on the red blood cell velocity and functional capillary density 30 and 90 minutes after reperfusion, compared with the control and vehicle-treated groups. Leukocyte-endothelial cell interactions were also affected by dehydroepiandrosterone treatment, as reflected by significant decreases in the numbers of sticking and transmigrating leukocytes 30 and 90 minutes after reperfusion. In dehydroepiandrosterone-treated animals, leukocytes exhibited lower levels of expression of adhesion molecules after the onset of ischemia, compared with the control groups. In this study, intravenous dehydroepiandrosterone administration reduced the activation of leukocytes and improved red blood cell velocity and capillary perfusion in the muscle flap microcirculation during ischemia-reperfusion injury. This protective effect was most likely the result of delayed expression of Mac-1 integrin, L-selectin, and CD44 molecules on leukocytes.
黏附分子通过增加白细胞的内皮黏附和外渗，促进缺血再灌注损伤。科学证据表明，术前使用脱氢表雄酮治疗可能保护微血管免受这种损伤，但其确切机制尚不清楚。本研究的目的是在大鼠提睾肌皮瓣模型中，研究术前脱氢表雄酮治疗对微循环血流动力学参数和黏附分子表达的影响。20只雄性大鼠被随机分为三个实验组。在第一组（n = 5）中，皮瓣未接受术前治疗。在第二组（n = 6）中，在诱导缺血前静脉注射脱氢表雄酮的载体丙二醇（30 mg/kg）。在第三组（n = 9）中，在诱导缺血前静脉注射脱氢表雄酮（30 mg/kg）。所有皮瓣均经历6小时缺血和90分钟再灌注。分析微循环变量（功能性毛细血管密度、皮瓣主要小动脉中的红细胞速度以及滚动、黏附和迁移的白细胞数量）、三种黏附分子（L-选择素、Mac-1整合素和CD44）的血液水平以及表达这些分子的白细胞数量。微循环参数分析显示，与对照组和载体治疗组相比，缺血前脱氢表雄酮治疗对再灌注后30分钟和90分钟的红细胞速度和功能性毛细血管密度具有显著的保护作用。脱氢表雄酮治疗也影响白细胞-内皮细胞相互作用，再灌注后30分钟和90分钟黏附和迁移的白细胞数量显著减少即反映了这一点。与对照组相比，在接受脱氢表雄酮治疗的动物中，缺血开始后白细胞上黏附分子的表达水平较低。在本研究中，静脉注射脱氢表雄酮可减少白细胞的激活，并改善缺血再灌注损伤期间皮瓣微循环中的红细胞速度和毛细血管灌注。这种保护作用很可能是白细胞上Mac-1整合素、L-选择素和CD44分子表达延迟的结果。
