Small interfering RNA targeting receptor for advanced glycation end products protects the rats from multibacterial sepsis
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.
KeywordsCecal 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.
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.
- 11.Buras JA, Holzmann B, Sitkovsky M (2005) Animal Models of sepsis: setting the stage. Nat Rev Drug Discov 4:854–865Google Scholar
- 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