Effect of curcumin on the expression of high mobility group box 1 and apoptotic neurons in hippocampus after global cerebral ischemia reperfusion in rats

OBJECTIVE: To explore the effects of curcumin on the expression of high mobility group box 1 (HMGB1) and apoptotic neurons in hippocampus after global cerebral ischemia/reperfusion in SD rats. METHODS: A total of 192 male SD rats were randomly divided into 4 groups: sham group (SH), ischemia-reperfusion group (IR), curcumin group (Cur) and solvent control group (SC). Bilateral vertebrate arteries were electrocauterized and bilateral common carotid arteries liberated in 3 ischemic groups. Isasteric curcumin solutions (200 mg/kg) or menstruum were injected intraperitoneally at 1 hour pre-ischemia in Cur and SC groups. The rats in each group were ligated for 15 minutes and then decapitated at 1, 3, 5 and 7 d post-reperfusion respectively. Cell morphology was observed on hematoxylin & eosin-stained slides. Apoptotic neurons were detected in CA1 region by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Western blot was used to make a semi-determination of HMGB1 expression. RESULTS: At each time point, the number of apoptotic neurons was much more in IR and SC groups than that in SH group (P < 0.05). And the number of apoptotic neurons at 1, 3, 5, 7 d post-reperfusion was only 41%, 57%, 65% and 70% in Cur group respectively (P < 0.05). The expressional level of HMGB1 in IR and SC groups was significantly lower at 1d post-reperfusion (0.685 ± 0.050; 0.695 ± 0.053 vs 0.977 ± 0.063, P < 0.05). And it was significantly higher at 3, 5, 7 d post-reperfusion in IR and SC groups than that in SH groups (1.360 ± 0.045/1.353 ± 0.045; 1.342 ± 0.046/1.338 ± 0.047; 1.319 ± 0.052/1.322 ± 0.035 vs 0.992 ± 0.031; 0.978 ± 0.090; 0.992 ± 0.075, P < 0.05). The level at 1 d post-reperfusion (0.842 ± 0.063) in Cur group was significantly higher than that in IR and SC groups but lower than that in SH group. And it was lower at 3, 5, 7 d post-reperfusion (1.125 ± 0.023, 1.098 ± 0.073, 1.087 ± 0.089) than those in IR and SC groups (P < 0.05). There was no significant difference of HMGB1expression level between IR and SC groups. CONCLUSION: The expression level of HMGB1 in hippocampus is significantly reduced at 1 d post-reperfusion. Then it significantly increases and a high level is maintained until 7 d after global cerebral ischemia/reperfusion. Curcumin can reduce hippocampal neuronal apoptosis and injury. Such an effect may be due to an inhibition of the synthesis and release of HMGB1.