Anti-RAGE antibody ameliorates severe thermal injury in rats through regulating cellular immune function  

作　　者：Xiao-mei ZHU Yong-ming YAO Li-tian ZHANG Ning DONG Yan YU Zhi-yong SHENG 

机构地区：[1]Department of Microbiology and Immunology, Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing100048, China

出　　处：《Acta Pharmacologica Sinica》2014年第9期1167-1176,共10页中国药理学报（英文版）

摘　　要：Aim： The receptor of advanced glycation end products （RAGE） participates in a variety of pathophysiological processes and inflammatory responses. The aim of this study was to investigate the therapeutic potential of an anti-RAGE neutralizing antibody for severe thermal injury in rats, and to determine whether the treatment worked via modulating cellular immune function. Methods： Full-thickness scald injury was induced in Wistar rats, which were treated with the anti-RAGE antibodY （1 mp=/kg, iv） at 6 h and 24 h after the injury. The rats were sacrificed on d 1, 3, 5, and 7. Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell （DC） and T cell cytokine profiles. The survival rate was analyzed up to d 7 after the injury. Results： Administration of the antibody significantly increased the 7 d survival rate in thermally injured rats （6.67% in the model group; 33.33% in anti-RAGE group）. Treatment with the antibody also attenuated the multiple organ dysfunction syndrome （MODS） following the thermal injury, as shown by significant decreases in the organ dysfunction markers, including serum ALT, AST, blood urea nitrogen, creatinine and CK-MB. Moreover, treatment with the antibody significantly promoted DC maturation and T cell activation in the spleens of thermally injured rats. Conclusion： Blockade of the RAGE axis by the antibody effectively ameliorated MODS and improved the survival rate in thermally injured rats, which may be due to modulation of cellular immune function.Aim： The receptor of advanced glycation end products （RAGE） participates in a variety of pathophysiological processes and inflammatory responses. The aim of this study was to investigate the therapeutic potential of an anti-RAGE neutralizing antibody for severe thermal injury in rats, and to determine whether the treatment worked via modulating cellular immune function. Methods： Full-thickness scald injury was induced in Wistar rats, which were treated with the anti-RAGE antibodY （1 mp=/kg, iv） at 6 h and 24 h after the injury. The rats were sacrificed on d 1, 3, 5, and 7. Blood and spleen samples were harvested to monitor organ function and to analyze dendritic cell （DC） and T cell cytokine profiles. The survival rate was analyzed up to d 7 after the injury. Results： Administration of the antibody significantly increased the 7 d survival rate in thermally injured rats （6.67% in the model group; 33.33% in anti-RAGE group）. Treatment with the antibody also attenuated the multiple organ dysfunction syndrome （MODS） following the thermal injury, as shown by significant decreases in the organ dysfunction markers, including serum ALT, AST, blood urea nitrogen, creatinine and CK-MB. Moreover, treatment with the antibody significantly promoted DC maturation and T cell activation in the spleens of thermally injured rats. Conclusion： Blockade of the RAGE axis by the antibody effectively ameliorated MODS and improved the survival rate in thermally injured rats, which may be due to modulation of cellular immune function.

关 键 词：RAGE anti-RAGE antibody burns thermal injury multiple organ dysfunction syndrome CYTOKINE inflammation IMMUNERESPONSE dendritic cell T cell 

分 类 号：S858.28[农业科学—临床兽医学] Q959.837[农业科学—兽医学]