The role of high mobility group box 1 in the signaling pathways of mouse intestinal ischemia-reperfusion injury / 中华外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of high mobility group box 1 (HMGB1) in the signaling pathway of mouse intestinal ischemia-reperfusion injury.</p><p><b>METHODS</b>Twenty-four Specific Pathogen free male C57BL / 6 mice were randomly divided into three groups (n = 8) the sham operation group (sham), the control group(control) and the HMGB1 antibody group (anti-HMGB1). The vehicle alone or anti-HMGB1 antibody(1 mg/kg, 0. 025%) was injected respectively via the caudal vein 30 min prior to ischemia in the control group or the anti-HMGB1 group. All mice were anesthetized,opened abdominal wall and exposed arteria mesenterica superior. The control group and the anti-HMGBl group underwent 60 min of mesenteric ischemia and 60 min of reperfusion and the sham group were merely opened abdominal wall for 120 min without ischemia-reperfusion. The levels of NF-κB p65, IL-6 and TNF-α in plasma and the activity of MPO in lung and liver and the morphological changes of lung and intestinal tissue were measured. The mRNA levels of HMGB1 and NF-κB were evaluated using real-time quantitative PCR and the protein levels of HMGB1 and NF-KB were evaluated using Western blot. The experimental data was analyzed using one-way analysis of variance.</p><p><b>RESULTS</b>The levels of IL-6, TNF-α and NF-κB p65 in plasma was significantly higher in the control group and the anti-HMGB1 group compared with the sham group (the sham group vs. the control group vs. the anti-HMGB1 group, NF-κB p65, 104. 64 ± 11. 89 228. 53 ± 24. 85 145. 00 ± 33. 63, F = 38. 036, P <0. 05; IL-6,50. 02 ± 6. 33104. 91 ± 31. 1862. 28 ± 6. 73, F = 49. 763, P < 0. 05; TNF-α, 43. 79 ± 4. 18 70. 81 ± 6. 97 52. 76 ± 5. 71, F = 34. 571, P < 0. 05). The increasing degree in the anti- HMGB1 group was significantly reduced compared with the control group (P <0. 05). The activity of MPO of liver and lung in the control group and the anti-HMGB1 group was significantly higher than those in the sham group (P <0. 05). Compared with the sham group, the degree of tissue injury in jejunum, ileum and lung was serious in the control group, and that in the anti-HMGB1 group was significantly lower than the control group. The expression of HMGB1 mRNA and NF-κB mRNA in the lung and the ileum in the sham group and the control group were all higher than the sham group (HMGB1 mRNA in lung sham group 1. 04 ± 0. 19 vs. control group 2. 25 ± 0. 18 vs. anti-HMGB1 group 1. 89 0. 18, F = 66. 203, P < 0. 05; in ileum 1. 14 ± 0. 54 vs. 6. 26 ± 0. 60 vs. 4. 93 0. 55, F = 133. 427, P < 0. 05; NF-κB mRNA in lung 1. 03 ± 0. 21 vs. 2. 04 ± 0. 29 vs. 1. 42 ± 0. 23, F =26. 229, P < 0. 05; ileum 1. 03 ± 0. 23 vs. 3. 71 ± 0. 53 vs. 2. 23 ± 0. 55, F = 50. 477, P <0. 05). Subjected to intestinal ischemia-reperfusion injury, the protein expression of HMGB1 and NF-κB in the lung, jejunum and ileum in the control group and the anti-HMGB1 group increased compared with the sham group(P <0. 05), but that was significantly lower in the anti-HMGB1 group than the control group (P <0. 05).</p><p><b>CONCLUSION</b>The administration of anti-HMGB1 antibodies may reduce the damage caused by ischemia-reperfusion effectively.</p>