A notable liver ischemia/reperfusion (I/R) injury is observed during liver transplantation, shock, trauma and other systemic diseases. The main aim of the present study was to evaluate the fact that HMGB1 acts as an early mediator of inflammation in hepatic injury and the potential of the miR-449b-5p mimic in the restoration of liver disorders. Herein, a miR-449b-5p-loaded spermidine/PLGA nanoparticle system was successfully formulated to improve the systemic delivery and performance of encapsulated miRNA. The major findings of the present study were as follows: (i) the HMGB1 levels were elevated upon the occurrence of I/R in vitro and in vivo; (ii) the inhibition of HMGB1 prevented the spread of inflammation; (iii) miR-449b-5p (PN-miR mimic) increased the cell viability of hepatic cells and decreased cell apoptosis; and (iv) the protective ability of the PN-miR mimic was attributed to the inhibition of the pNF-κB and p-p65 pathways. Compared to the case of the I/R group, the serum AST and ALT levels were significantly reduced in the group treated with miR-449b-5p (PN-miR mimic), indicating the extent of reduction in liver inflammation. The present study highlighted the importance of miR-449b-5p in the treatment of hepatic injury and could serve as a guide to effectively attenuate liver disorders. The application of the proposed nanoparticle system in the systemic delivery of miR-449b-5p further enhances the prospect of this treatment strategy.
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