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Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.


ABSTRACT: Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24 h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3 h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6 h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3 h. Histological analysis revealed lung injury at 6 and 24 h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.

SUBMITTER: Matsumoto H 

PROVIDER: S-EPMC5613014 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

Matsumoto Hisatake H   Matsumoto Naoya N   Shimazaki Junya J   Nakagawa Junichiro J   Imamura Yukio Y   Yamakawa Kazuma K   Yamada Tomoki T   Ikeda Mitsunori M   Hiraike Hiroko H   Ogura Hiroshi H   Shimazu Takeshi T  

Scientific reports 20170925 1


Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE anti  ...[more]

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