RNA interference targeting RelB attenuates liver ischemia/reperfusion injury

Background: RNA interference targeting RelB can significantly attenuate ischemia/reperfusion (I/R)-induced renal dysfunction, but its roles in liver I/R injury remain to be defined. We have investigated whether siRNA targeting of RelB in liver could also elicit protection against I/R injury.

Materials and methods: A RelB miRNA RNAi expression plasmid, a scrambled plasmid, or phosphate-buffered saline (50 μg of the plasmid diluted in phosphate-buffered saline, 8% wt/vol) were rapidly injected, within 6-8 s, into mouse tail veins 24 h before liver I/R. Mice were subjected to 30 min of 70% hepatic ischemia or to a sham operation. Six h after reperfusion, blood and liver tissue samples were collected for subsequent assays.

Results: The expression level of RelB was reduced in the RelB RNAi group compared with the control group, while it was increased in the I/R group. In the sham group, malondialdehyde, myeloperoxidase (MPO), and superoxide dismutase serum levels were almost the same, but the alanine aminotransferase level in the untreated group was 20- to 25-fold lower than in the other groups. In I/R-treated mice, although alanine aminotransferase, malondialdehyde, and MPO serum levels in the RelB RNAi group were lower than in other groups, all were higher than in the sham group. Silencing RelB could inhibit the decrease of superoxide dismutase activity and the upregulation of MPO and tumor necrosis factor α induced by I/R injury.

Conclusions: Silencing RelB can protect the liver against I/R-induced damage. Therefore, it is a promising therapeutic target for protection against I/R injury in the liver.