Background: 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.
Aims: 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.
Methods: 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.
Results: 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.
Conclusions: Targeting RAGE by siRNA might attenuate hyperinflammation, improve survival rate, and offer new therapeutic options for sepsis.
Keywords: Cecal ligation and puncture; Receptor for advanced glycation end products; Sepsis; Small interfering RNA.