Irish Journal of Medical Science (1971 -)

, Volume 187, Issue 1, pp 225–229 | Cite as

Small interfering RNA targeting receptor for advanced glycation end products protects the rats from multibacterial sepsis

  • X. Zhao
  • Y. N. Liao
  • Q. HuangEmail author
Brief Report



Sepsis is a major challenge in clinical medicine, and treatment options are limited. Recently, the receptor for advanced glycation end products (RAGE) appears to be an excellent target for new therapeutic agents.


The objective of this study is to investigate the effect of small interfering RNA (siRNA) targeting RAGE on the outcome of multibacterial sepsis induced by cecal ligation and puncture (CLP) in a rat model.


A vector-based RAGE-targeted siRNA expression system (Psilencer-siRNA) was constructed and injected into rats via the jugular vein catheter after CLP injury. The RAGE expression in livers, survival rate, and plasma cytokine levels after CLP were compared between Psilencer-siRNA treated and control rats.


The expression of RAGE in livers which was upregulated after CLP injury was greatly curtailed by Psilencer-siRNA administration. Compared to control rats, the Psilencer-siRNA-treated rats had significantly higher survival rate (p < 0.05) and markedly decreased plasma cytokine levels (p < 0.001) after CLP.


Targeting RAGE by siRNA might attenuate hyperinflammation, improve survival rate, and offer new therapeutic options for sepsis.


Cecal ligation and puncture Receptor for advanced glycation end products Sepsis Small interfering RNA 


Compliance with ethical standards


This study was funded by the National Natural Scientific Foundation of China (Grant number: 81370514).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Jinling Hospital, Medical School of Nanjing University and was performed in accordance with the Guide for Care and Use of Laboratory Animals from National Institutes of Health. This article did not contain any studies with human participants performed by any of the authors.


  1. 1.
    Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ et al (2013) Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev 93:1247–1288. doi: 10.1152/physrev.00037.2012 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Gotts JE, Matthay MA (2016) Sepsis: pathophysiology and clinical management. BMJ 353:i1585. doi: 10.1136/bmj.i1585 CrossRefPubMedGoogle Scholar
  3. 3.
    van Zoelen MA, Achouiti A, van der Poll T (2011) The role of receptor for advanced glycation endproducts (RAGE) in infection. Crit Care 15:208. doi: 10.1186/cc9990 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Liliensiek B, Weigand MA, Bierhaus A et al (2004) Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response. J Clin Invest 113:1641–1650CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lutterloh EC, Opal SM, Pittman DD et al (2007) Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection. Crit Care 11:R122CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Jeong SJ, Lim BJ, Park S et al (2012) The effect of sRAGE-Fc fusion protein attenuates inflammation and decreases mortality in a murine cecal ligation and puncture model. Inflamm Res 61:1211–1218. doi: 10.1007/s00011-012-0518-7 CrossRefPubMedGoogle Scholar
  7. 7.
    McCaffrey AP, Meuse L, Pham TT et al (2002) RNA interference in adult mice. Nature 418:38–39CrossRefPubMedGoogle Scholar
  8. 8.
    Pushparaj PN, Aarthi JJ, Manikandan J et al (2008) siRNA, miRNA, and shRNA: in vivo applications. J Dent Res 87:992–1003CrossRefPubMedGoogle Scholar
  9. 9.
    Rittirsch D, Huber-Lang MS, Flierl MA et al (2009) Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc 4:31–36. doi: 10.1038/nprot.2008.214 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lei M, Jiao H, Liu T et al (2011) siRNA targeting mCD14 inhibits TNF-α, MIP-2, and IL-6 secretion and NO production from LPS-induced RAW264.7 cells. Appl Microbiol Biotechnol 92:115–124. doi: 10.1007/s00253-011-3371-7 CrossRefPubMedGoogle Scholar
  11. 11.
    Buras JA, Holzmann B, Sitkovsky M (2005) Animal Models of sepsis: setting the stage. Nat Rev Drug Discov 4:854–865Google Scholar
  12. 12.
    Creagh-Brown BC, Quinlan GJ, Evans TW et al (2010) The RAGE axis in systemic inflammation, acute lung injury and myocardial dysfunction: an important therapeutic target? Intensive Care Med 36:1644–1656. doi: 10.1007/s00134-010-1952-z 

Copyright information

© Royal Academy of Medicine in Ireland 2017

Authors and Affiliations

  1. 1.Research Institute of General SurgeryJinling Hospital, Medical School of Nanjing UniversityNanjingChina

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