Cordeiro P G, Mastorakos D P, Hu Q Y, Kirschner R E
Division of Plastic and Reconstructive Surgery, Memorial Sloan-Kettering Cancer Center, New York, N.Y., USA.
Plast Reconstr Surg. 1997 Oct;100(5):1227-33. doi: 10.1097/00006534-199710000-00023.
The objective of this study was to examine whether the administration of L-arginine, a precursor of nitric oxide and substrate of nitric oxide synthase, prior to reperfusion could lead to decrease in neutrophil-mediated tissue injury and improved flap survival. Epigastric island skin flaps were elevated in 70 rats and rendered ischemic. Thirty minutes prior to reperfusion, the rats were treated with intraperitoneal saline (n = 15), L-arginine (n = 15), D-arginine (n = 15), or N omega-nitro-L-arginine methylester plus L-arginine in equimolar amounts (n = 15). Flap survival at 7 days and neutrophil counts at 24 hours were evaluated. Flap necrosis as expected in the sham group of animals (n = 10) was 0.0 percent, while the control (saline-treated) animals had 59.6 percent necrosis. Animals treated with L-arginine demonstrated a significant decrease in flap necrosis to 12.7 percent. This protective effect was almost completely negated by N omega-nitrol-L-arginine methylester, which significantly increased flap necrosis to 49.3 percent and was much less pronounced with D-arginine (28.6 percent). Neutrophil counts were significantly decreased in flaps from L-arginine-treated and sham animals versus both saline and N omega-nitro-L-arginine methylester-treated groups. We conclude that administration of L-arginine prior to reperfusion can significantly reduce the extent of flap necrosis and flap neutrophil counts due to ischemia-reperfusion injury. This protective effect is completely negated by nitric oxide synthase inhibition. Since L-arginine reduces the number of neutrophils within the flap and the extent of flap necrosis only in the presence of active nitric oxide synthase, we hypothesize that this protective effect of L-arginine on ischemia-reperfusion injury is secondary to a nitric oxide-mediated suppression of neutrophil-mediated injury.
本研究的目的是检验在再灌注前给予一氧化氮的前体及一氧化氮合酶的底物L-精氨酸是否会导致中性粒细胞介导的组织损伤减少以及皮瓣存活率提高。在70只大鼠中掀起上腹部岛状皮瓣并使其缺血。在再灌注前30分钟，给大鼠腹腔注射生理盐水（n = 15）、L-精氨酸（n = 15）、D-精氨酸（n = 15）或等摩尔量的Nω-硝基-L-精氨酸甲酯加L-精氨酸（n = 15）。评估7天时的皮瓣存活率和24小时时的中性粒细胞计数。假手术组动物（n = 10）的皮瓣坏死率如预期为0.0%，而对照组（生理盐水处理）动物的坏死率为59.6%。用L-精氨酸处理的动物皮瓣坏死率显著降低至12.7%。Nω-硝基-L-精氨酸甲酯几乎完全消除了这种保护作用，它使皮瓣坏死率显著增加至49.3%，而D-精氨酸的作用则不太明显（28.6%）。与生理盐水和Nω-硝基-L-精氨酸甲酯处理组相比，L-精氨酸处理组和假手术组动物皮瓣中的中性粒细胞计数显著降低。我们得出结论，再灌注前给予L-精氨酸可显著降低缺血-再灌注损伤所致的皮瓣坏死程度和皮瓣中性粒细胞计数。一氧化氮合酶抑制可完全消除这种保护作用。由于L-精氨酸仅在有活性一氧化氮合酶存在时才会减少皮瓣内的中性粒细胞数量和皮瓣坏死程度，我们推测L-精氨酸对缺血-再灌注损伤的这种保护作用继发于一氧化氮介导的对中性粒细胞介导损伤的抑制。
