Meldrum D G, Stephenson L L, Zamboni W A
Microsurgery Research Laboratory, Division of Plastic Surgery, University of Nevada School of Medicine, Las Vegas 89102, USA.
Plast Reconstr Surg. 1999 Mar;103(3):935-40. doi: 10.1097/00006534-199903000-00025.
The involvement of nitric oxide in ischemia-reperfusion injury remains controversial and has been reported to be both beneficial and deleterious, depending on the tissue and model used. This study evaluated the effects of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) and the substrate for nitric oxide synthase, L-arginine on skeletal muscle necrosis in a rat model of ischemia-reperfusion injury. The rectus femoris muscle in male Wistar rats (250 to 500 g) was isolated on its vascular pedicle and subjected to 4 hours of complete arteriovenous occlusion. The animals were divided into five groups: (1) sham-raised control, no ischemia, no treatment (n = 6); (2) 4 hours of ischemia (n = 6); (3) vehicle control, 4 hours of ischemia + saline (n = 6); (4) 4 hours of ischemia + L-arginine infusion (n = 6); and (5) 4 hours of ischemia + L-NAME infusion (n = 6). The infusions (10 mg/kg) were administered into the contralateral femoral vein beginning 5 minutes before reperfusion and during the following 30 to 45 minutes. Upon reperfusion, the muscle was sutured in its anatomic position and all wounds were closed. The percentage of muscle necrosis was assessed after 24 hours of reperfusion by serial transections, nitroblue tetrazolium staining, digital photography, and computerized planimetry. Sham (group 1) animals sustained baseline necrosis of 11.9 +/- 3.0 (percentage necrosis +/- SEM). Four hours of ischemia (group 2) significantly increased necrosis to 79.2 +/- 1.4 (p < 0.01). Vehicle control (group 3) had no significant difference in necrosis (81.17 +/- 5.0) versus untreated animals subjected to 4 hours of ischemia (group 2). Animals treated with L-arginine (group 4) had significantly reduced necrosis to 34.6 +/- 7.5 versus untreated (group 2) animals (p < 0.01). Animals infused with L-NAME (group 5) had no significant difference in necrosis (68.2 +/- 6.7) versus untreated (group 2) animals. L-Arginine (nitric oxide donor) significantly decreased the severity of muscle necrosis in this rat model of ischemia-reperfusion injury. L-arginine is known to increase the amount of nitric oxide through the action of nitric oxide synthase, whereas L-NAME, known to inhibit nitric oxide synthase and decrease nitric oxide production, had comparable results to the untreated 4-hour ischemia group. These results suggest that L-arginine, presumably through nitric oxide mediation, appears beneficial to rat skeletal muscle subjected to ischemia-reperfusion injury.
一氧化氮在缺血再灌注损伤中的作用仍存在争议，据报道，根据所使用的组织和模型不同，其作用既有有益的一面，也有有害的一面。本研究评估了一氧化氮合酶抑制剂N（G）-硝基-L-精氨酸甲酯（L-NAME）和一氧化氮合酶底物L-精氨酸对缺血再灌注损伤大鼠模型骨骼肌坏死的影响。将雄性Wistar大鼠（250至500克）的股直肌在其血管蒂上分离出来，并进行4小时的完全动静脉闭塞。动物被分为五组：（1）假手术对照，无缺血，未治疗（n = 6）；（2）缺血4小时（n = 6）；（3）溶剂对照，缺血4小时+生理盐水（n = 6）；（4）缺血4小时+L-精氨酸输注（n = 6）；（5）缺血4小时+L-NAME输注（n = 6）。在再灌注前5分钟开始，并在接下来的30至45分钟内，将输注液（10毫克/千克）注入对侧股静脉。再灌注时，将肌肉缝合到其解剖位置，所有伤口均缝合。在再灌注24小时后，通过连续横切、硝基蓝四氮唑染色、数码摄影和计算机化平面测量法评估肌肉坏死的百分比。假手术组（第1组）动物的基线坏死率为11.9±3.0（坏死百分比±标准误）。缺血4小时（第2组）显著增加坏死率至79.2±1.4（p < 0.01）。溶剂对照组（第3组）与未治疗的缺血4小时动物（第2组）相比，坏死率无显著差异（81.17±5.0）。用L-精氨酸治疗的动物（第4组）与未治疗的动物（第2组）相比，坏死率显著降低至34.6±7.5（p < 0.01）。输注L-NAME的动物（第5组）与未治疗的动物（第2组）相比，坏死率无显著差异（68.2±6.7）。在这个缺血再灌注损伤大鼠模型中，L-精氨酸（一氧化氮供体）显著降低了肌肉坏死的严重程度。已知L-精氨酸通过一氧化氮合酶的作用增加一氧化氮的量，而L-NAME已知可抑制一氧化氮合酶并减少一氧化氮的产生，其结果与未治疗的4小时缺血组相当。这些结果表明，L-精氨酸可能通过一氧化氮介导，对遭受缺血再灌注损伤的大鼠骨骼肌似乎有益。
