Zhang Xiao-tian, Yao Yong-ming, Huang Li-feng, Yu Yan
Burns Institute, First Hospital Affiliated to The PLA General Hospital, Beijing 100037, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008 Sep;20(9):523-6.
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.
Male Wistar rats were subjected to 30% full thickness scald injury followed by delayed resuscitation (40 ml/kg lactated Ringer's 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 postburn days 1, 3, 5 and 7 respectively, and blood samples were obtained to determine parameters reflecting hepatic, renal as well as cardiac functions.
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 up to 7 days after burns (P < 0.05 or P < 0.01).
Anti-RAGE antibody could obviously improve the survival in rats with burn injury with delayed resuscitation, and it seems to be able to prevent the development of multiple organ dysfunction secondary to severe burns.
观察晚期糖基化终末产物受体（RAGE）抗体治疗对严重烧伤大鼠多器官功能障碍及死亡率的影响，并探讨其保护作用的机制。
雄性Wistar大鼠行30%全层烫伤，随后延迟复苏（伤后6小时腹腔注射40 ml/kg乳酸林格氏液进行复苏）。130只大鼠随机分为假烫伤组（n = 10）、烫伤组（n = 60）和抗RAGE抗体治疗组（n = 60）。抗RAGE抗体（1 mg/kg）于烧伤后6小时和24小时经阴茎背静脉给予。每天记录各组大鼠伤后7天内的存活率。72只大鼠随机分为假烫伤组、烫伤组和抗RAGE抗体治疗组（n = 24）。每组大鼠再进一步分为4个亚组，每组6只。分别于伤后第1、3、5和7天处死，取血样测定反映肝、肾及心功能的指标。
与假烫伤组相比，烫伤组大鼠伤后1 - 7天血清丙氨酸氨基转移酶（ALT）及天冬氨酸氨基转移酶（AST）、肌酐（Cr）、血尿素氮（BUN）、肌酸激酶MB同工酶（CK - MB）水平显著升高（P < 0.05或P < 0.01），血清ALT、AST、Cr及BUN水平于伤后第3天达峰值。然而，抗RAGE抗体治疗后，上述指标水平与烫伤组相比明显降低，血清AST水平在整个观察期内显著降低，而其他指标在伤后1 - 5天明显改善（P < 0.05或P < 0.01）。此外，与烫伤大鼠相比，抗RAGE抗体治疗的烫伤大鼠在烧伤后7天内每天的存活率均显著提高（P < 0.05或P < 0.01）。
抗RAGE抗体可明显提高延迟复苏烧伤大鼠的存活率，似乎能够预防严重烧伤后继发的多器官功能障碍的发生。
