Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
Shock. 2009 Dec;32(6):586-92. doi: 10.1097/SHK.0b013e3181a2b886.
Free radicals play an important role in the inflammatory process of sepsis. We hypothesized that edaravone, a novel free radical scavenger, can suppress pathophysiological events and prolong survival in a neonatal sepsis cecal ligation and perforation (CLP) model. Of 32 3-day-old anesthetized and mechanically ventilated piglets, 11 received CLP only, 10 received CLP and edaravone treatment starting 30 min after CLP, and 11 constituted a sham (control) group. Mean arterial pressure (MAP), heart rate, cardiac output, arterial blood gas, serum total hydroperoxide, nitrite and nitrate, TNF-alpha, and high-mobility group box 1 (HMGB1) were measured before CLP and at 1, 3, and 6 h after CLP. Compared with the CLP group, the edaravone group showed higher MAP at 6 h, lower heart rate at 1 and 3 h, lower total hydroperoxide at 1 h, lower nitrite and nitrate at 3 and 6 h, and higher (although not significantly so) mean cardiac output at 1, 3, and 6 h. TNF-alpha elevation was delayed from 1 h in the CLP group to 3 h in the edaravone group. In the edaravone group, HMGB1 did not change significantly at any time, whereas in the CLP group, it increased at 6 h. Survival times were longer in the edaravone group than in the CLP group (15.4 +/- 1.4 vs. 10.2 +/- 1 h; P < 0.005). In addition, each of the serial dilutions of edaravone had a higher biological antioxidant potential than tempol does. In conclusion, edaravone suppressed free radicals, delayed the TNF-alpha surge, and prevented HMGB1 elevation, thereby maintaining MAP and prolonging survival time in a neonatal sepsis CLP model.
自由基在脓毒症的炎症过程中发挥重要作用。我们假设，新型自由基清除剂依达拉奉可抑制新生脓毒症盲肠结扎穿孔（CLP）模型中的病理生理事件并延长其生存时间。将 32 只 3 日龄麻醉和机械通气的仔猪随机分为三组：CLP 组（11 只）仅接受 CLP 手术，CLP+依达拉奉组（10 只）在 CLP 后 30 分钟开始接受依达拉奉治疗，假手术（对照）组（11 只）仅接受开腹和关腹操作。在 CLP 前和 CLP 后 1、3 和 6 小时测量平均动脉压（MAP）、心率、心输出量、动脉血气、血清总过氧化物、亚硝酸盐和硝酸盐、肿瘤坏死因子-α（TNF-α）和高迁移率族蛋白 1（HMGB1）。与 CLP 组相比，依达拉奉组在 6 小时时 MAP 较高，1 和 3 小时时心率较低，1 小时时总过氧化物较低，3 和 6 小时时亚硝酸盐和硝酸盐较低，1、3 和 6 小时时心输出量（虽然差异无统计学意义）较高。TNF-α 的升高从 CLP 组的 1 小时延迟至依达拉奉组的 3 小时。在依达拉奉组，HMGB1 任何时间均无明显变化，而在 CLP 组，HMGB1 在 6 小时时升高。依达拉奉组的生存时间长于 CLP 组（15.4 ± 1.4 比 10.2 ± 1 小时；P < 0.005）。此外，依达拉奉的每个连续稀释液的生物抗氧化潜力均高于 Tempo1。总之，依达拉奉抑制自由基，延迟 TNF-α 激增，并防止 HMGB1 升高，从而维持 MAP 并延长新生脓毒症 CLP 模型的生存时间。
