MG132 Ablates Liver Injury Induced by Intestinal Ischemia-Reperfusion Through Nrf2 and HO-1

AIM: To investigate the effect of MG132 upregulating the expression of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in liver injury induced by intestinal ischemia-reperfusion (IR). METHODS: Rats were divided randomly into four groups: control group, IR group, control+ MG132 pretreatment group and IR+ MG132 pretreatment group (n=8 in each group). The intestinal IR model was established by clamping the superior mesenteric artery (SMA) for 1 h and reperfusing for 2 h. Pretreatment groups were given MG132 0.5 mg/kg via intraperitoneal administration 30 min before ischemia. The control group only received a laparotomy and isolation of the SMA without occlusion. Intestinal and liver histology was investigated. Serum levels of TNF-alpha, ALT, AST, LDH and 26S proteasome were measured. Liver tissue SOD and MPO activities were assayed. The liver Nrf2 and HO-1 levels were determined by immunohistochemical analysis and Western blot analysis. RESULTS: Compared to the control group, there were several changes in the IR group as follows: (1) Obvious edema, exudation and inflammatory cell infiltration were observed in liver and intestinal tissues (P<0.01 for both); (2) Liver SOD activity was decreased (P<0.01), while liver MPO activity was increased (P<0.01); (3) Serum TNF-alpha, ALT, AST and LDH were significantly enhanced (P< 0.01 for all); (4) Liver tissue Nrf2 and HO-1 protein expressions were increased (P<0.01 for both). Compared to the control group, there were se-veral changes in the control+MG132 pretreatment group as follows:(1) Liver SOD activity was increased (P<0.05); (2) The 26S proteasome level was decreased (P<0.05); (3) Liver tissue Nrf2 and HO-1 protein expressions were increased (P<0.01 for both). Compared to the IR group, there were several changes in the IR+MG132 pretreatment group as follows: (1) Liver and intestinal tissue pathological scores of injury were reduced (P<0.01 for both); (2) Liver SOD activity was increased (P<0.01), while liver MPO activity was decreased (P<0.05); (3) Serum TNF-alpha, ALT, AST and LDH levels were decreased (P<0.01, P<0.01, P<0.05 and P<0.05, respectively); (4) The 26S proteasome level was decreased (P<0.01); (5) Liver tissue Nrf2 and HO-1 protein expressions were increased (P<0.01 for both). CONCLUSIONS: MG132 pretreatment provided a significant protective effect in liver injury induced by intestinal IR in rats, which was attributed to protection through the activation of Nrf2 and HO-1