目的观察拮抗晚期糖基化终末产物受体(RAGE)对烫伤延迟复苏动物多器官功能及死亡率的影响,并探讨其作用机制。方法选取雄性Wistar大鼠,采用重度烫伤延迟复苏模型(30%总体表面积Ⅲ度烫伤)。实验分为两部分。死亡率观察:130只大鼠被随机分为假手术组(n=10)、烫伤组(n=60)及RAGE抗体治疗组(n=60),观察伤后7d内每日动物的存活率。器官功能观察:72只大鼠被随机分为假手术组(n=24)、烫伤组(n=24)及RAGE抗体治疗组(n=24),于伤后1、3、5和7d各活杀6只动物,取血,用全自动生化分析仪测定肝、肾和心脏器官功能指标。结果烫伤组伤后1~7d,大鼠血中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肌酐(Cr)、尿素氮(BUN)及肌酸激酶同工酶(CK—MB)水平均显著高于假手术组(P〈0.05或P〈0.01),其中ALT、AST、Cr及BUN水平均于伤后3d达峰值;给予RAGE抗体治疗可不同程度降低烫伤动物血中各指标水平,其中AST在伤后1~7d显著下降,余指标在伤后1~5d均明显改善(P〈0.05或P〈0.01)。RAGE抗体治疗组伤后7d内每日大鼠存活率显著高于烫伤组(P〈0.05或P〈0.01)。结论RAGE抗体干预能明显改善重度烫伤延迟复苏大鼠的预后,并对重要器官功能具有显著保护作用。
Objective To observe the effect of treatment with anti-receptor for advanced glycation end products (RAGE) antibody on multiple organ dysfunction and mortality in rats after severe burn injury, and investigate the mechanisms underlying its protective effect. Methods Male Wistar rats were subjected to 30% full thickness scald injury followed by delayed resuscitation (40 ml/kg lactated Ringerfs solution resuscitation administered intraperitoneally 6 hours after the injury). One hundred and thirty rats were randomly divided into sham scald group (n= 10), scald group (n = 60) and anti-RAGE antibody treatment group (n= 60). Anti-RAGE antibody (1 mg/kg) was given via dorsal penile vein at 6 and 24 hours after burn injury. Survival rate of rats in each group was recorded daily up to 7 days after the injury. Seventy-two rats were randomly divided into sham scald group, scald group and anti-RAGE antibody treatment group (n= 24). Rats in each group were further divided into four subgroups of 6 rats each. They were sacrificed on posthurn days 1, 3, 5 and 7 respectively, and blood samples were obtained to determine parameters reflecting hepatic, renal as well as cardiac functions. Results Compared with the sham scald group, levels of serum alanine amino transferase (ALT), aspartate amino transferase (AST), creatinine (Cr), blood urea nitrogen (BUN), and MB isoenzyme of creatine kinase (CK-MB) were significantly elevated during postburn days 1-7 (P〈0.05 or P〈0.01), and serum levels of ALT, AST, Cr, and BUN peaked on postburn day 3. Treatment with anti-RAGE antibody, however, the levels of above parameters were markedly lowered compared with the scald group, and serum AST levels were significantly lowered during whole observational period, while other parameters were markedly improved during postburn days 1 - 5 (P〈0.05 or P〈0.01). Moreover, survival rates of the scald rats treated with anti-RAGE antibody were significantly raised compared with the scald rats daily