MG132 Protects Liver Injury Induced By Intestinal Ischemia Reperfusion Through Nrf2/Keap1-ARE Pathway

Objective:To investigate the effect of the proteasome inhibitor MG-132 on neutrophil infiltration, HO-1 and Nrf2 expression in liver injury induced by intestinal ischaemia-reperfusion (IR).Methods:Thirty two male Sprague Dawley rats were randomly divided into 4 groups as control, IR, control+MG132 pretreatment and IR+MG132 pretreatment groups (n=8 in each group). The IR model was established by clamping superior mesenteric artery (SMA) for 1 hour and reperfusion for 2 hours. Pretreatment groups at 30 minutes before ischemia, respectively 0.5 mg/kg MG132 abdominal injection, the control group carried out only laparotomy and isolation of the SMA without occlusion. The end of reperfusion, rats of blood, liver and intestine were investigated.Results:Compared with the control group, changes in IR group as (1) Liver and intestinal tissue were obvious edema, exudation and inflammatory cell infiltration (P<0.01, P<0.01); (2) Liver SOD activity was decreased (P<0.01). Liver MPO activity was increased (P<0.01); (3) Serum TNF-a, IL-6, ALT, AST and LDH were significantly enhanced (P<0.01, P<0.01, P<0.01, P<0.01, P<0.01); (4) 26S proteasome lever in no significant changes (P>0.05); (5) Liver tissue of Nrf2 and HO-1 protein expression were increased (P<0.01, P<0.01). Compared with the control group, changes in control+MG132 pretreatment group as (1) Liver SOD activity was increased (P<0.05); (2) 26S proteasome level was decreased (P<0.05); (3) Liver tissue of Nrf2 and HO-1 protein expression were increased (P<0.01, P<0.01). Compared with the IR group changes in IR+MG132 pretreatment group as (1) Liver and intestine tissue pathological scores of injury significantly were reduced (P<0.01, P<0.01); (2) Liver SOD activity was increased (P<0.01), MPO activity was decreased (P<0.05); (3) Serum TNF-a, IL-6, ALT, AST and LDH levels were decreased (P<0.01, P<0.05, P<0.01, P<0.05, P<0.05); (4) 26S proteasome lever was decreased (P<0.01); (5) Liver tissue of Nrf2 and HO-1 protein expression were increased (P<0.01,P<0.01).Conclusions:(1) Intestinal IR may result in severe liver injury; (2) MG132 pretreatment has significantly protective effect on liver injury induced by intestinal IR, attributable to the protection through activation of Nrf2 and HO-1.