AbstractObjective To investigate the effect of high volume hemofiltration (HVHF) on the gene expression of endoplasmic reticulum stress markers in multiple organ dysfunction syndrome (MODS) dogs.  Methods MODS model of Beagle dogs were established by a “two-hit” injury and then randomly divided into two groups, HVHF group (n=6) and MODS group (n=6). Blood samples were drawn in the two groups at preoperative (T1) and after injection of endotoxin for 0h (T2), 6h (T3), 12h (T4) and 24 h (T5). Quantitative real-time PCR was used to measure caspase-12 mRNA levels in liver, kidney and lung. In addition, dog serum samples were applied to human umbilical venous endothelial cells (HUVECs) to induce endoplasmic reticulum stress, and the expression of caspase-12 and apoptosis in HUVECs were then assayed before and after down-regulation of caspase-12 expression by siRNA interference. Results Caspase-12 mRNA levels in kidney and lung were lower in HVHF group than in MODS group (P0.05), but the mRNA levels in liver was similar between the two groups (P>0.05). In HUVECs before siRNA interference, caspase-12 mRNA, caspase-12 protein and apoptosis decrease more by T2-T5 samples from HVHF group than by those from MODS group (P0.01). In HUVECs induced with serum samples from HVHF group and MODS group, caspase-12 mRNA, caspase-12 protein and apoptosis decrease more in HUVECs after the siRNA interference than in those before the siRNA interference (P0.01). Conclusion The endoplasmic reticulum stress pathway plays an important role in the evolution processes of MODS. RNA interference may become a new therapeutic modality for the treatment of MODS.