Shin M S, Angel M F, Im M J, Manson P N
Division of Plastic, Reconstructive and Maxillofacial Surgery, Johns Hopkins University School of Medicine, Baltimore, Md.
Plast Reconstr Surg. 1994 Oct;94(5):661-6. doi: 10.1097/00006534-199410000-00014.
The effect of 21-aminosteroid, a lazaroid (U74389F), on tissue injury after secondary ischemia was evaluated in 3 x 5 cm island skin flaps in male Sprague-Dawley rats (n = 30). Primary ischemia was produced by arteriovenous occlusion for 1 hour. Eighteen hours later, secondary ischemia was inflicted by 4-hour venous occlusion. The treatment group received intravenous lazaroid (3 mg/kg) 30 minutes before the start of secondary ischemia. The control group received the same volume of citrate buffer vehicle using the same route and schedule. Skin-flap survival was an all-or-none phenomenon and assessed at 7 days after secondary ischemia. Malondialdehyde (MDA) content was measured to determine the occurrence of lipid peroxidation. Myeloperoxidase (MPO) activity was assayed to assess the degree of neutrophil infiltration. Treatment with this lazaroid significantly improved the survival rate from 0 percent (0 of 13) to 53 percent (9 of 17) (p < 0.01). Malondialdehyde content was 62 +/- 10 (mean +/- SEM, n = 4) pmol/mg dry weight in normal skin. Malondialdehyde increased by 3 times normal in the flaps destined to survive and by 13 times in the flaps destined to undergo necrosis (p < 0.001). Myeloperoxidase activity was negligible in normal skin. At the end of secondary ischemia, the flaps destined to survive exhibited a high myeloperoxidase activity. The flaps destined to necrosis showed the enzyme activity 2.2 times more than surviving flaps (p < 0.01). The results suggest that the lazaroid U74389F may improve survival by attenuating neutrophil infiltration and by reducing lipid peroxidation.
在雄性斯普拉格-道利大鼠（n = 30）的3×5平方厘米岛状皮瓣中，评估了21-氨基类固醇（一种拉扎罗类药物，U74389F）对继发性缺血后组织损伤的影响。通过动静脉闭塞1小时造成原发性缺血。18小时后，通过静脉闭塞4小时造成继发性缺血。治疗组在继发性缺血开始前30分钟静脉注射拉扎罗类药物（3毫克/千克）。对照组通过相同途径和时间表接受相同体积的柠檬酸盐缓冲液载体。皮瓣存活是一种全或无的现象，并在继发性缺血后7天进行评估。测量丙二醛（MDA）含量以确定脂质过氧化的发生情况。测定髓过氧化物酶（MPO）活性以评估中性粒细胞浸润程度。用这种拉扎罗类药物治疗可使存活率从0%（13例中的0例）显著提高到53%（17例中的9例）（p < 0.01）。正常皮肤中丙二醛含量为62±10（平均值±标准误，n = 4）皮摩尔/毫克干重。在注定存活的皮瓣中，丙二醛增加到正常水平的3倍，在注定坏死的皮瓣中增加到13倍（p < 0.001）。正常皮肤中髓过氧化物酶活性可忽略不计。在继发性缺血结束时，注定存活的皮瓣表现出高髓过氧化物酶活性。注定坏死的皮瓣显示的酶活性比存活皮瓣高2.2倍（p < 0.01）。结果表明，拉扎罗类药物U74389F可能通过减轻中性粒细胞浸润和减少脂质过氧化来提高存活率。
