The effect of curcumin against cerebral ischemia-induced neuronal apoptosis of SD rats

Abstract

Objective To investigate the effect and molecular mechanisms of curcumin against ischemia reperfusion injury in hippocampus of SD rats,and to provide the experimental and theoretical basis of curcumin in clinical work.Methods One hundred and twenty male SD rats were randomly divided into five groups:sham group ( sham),ischemia-reperfusion group ( I/R),curcumin group with dosage of 30 mg/kg (Cur30),100 mg/kg (Cur100) and 300 mg/kg (Cur300).Isasteric curcumin solutions or menstruum were intraperitoneally injected at 1st h before ischemia.Each rat was ligated for 15 min and reperfused except sham group.Rats were killed at 2 h,6 h,1 day,and 3 day after reperfusion in each group.Immunohistochemistry was used to observe the expression of B lymphocytes/leukemia-2 (bcl-2) and bax,and the TdT-mediated dUTP nick end labeling (TUNEL) method was used to count the apoptotic neurons.Results As compared with sham group,the expression of bcl-2 and bax in CA1 regions began to increase at 2 h after reperfusion,and reached the peak at 1 days,then decreased,and the expression level decreased to normal level at 3 day.The expression level of bcl-2 in CA1 regions was higher in Cur30,Cur100and Cur300 groups at 6 h,1 day and 3 day after reperfusion than in I/R group ( all P ＜0.05 ).The intensity of the expression was Cur100 ＞ Cur30 ＞ Cur300 at 1 day and 3 day after reperfusion (P ＜0.05).The expression of bax was higher in I/R group than in Cur300,Cur30 and Cur100 groups (P ＜0.05),and that of bax was lower in Cur100 group at 1 day and 3 day after reperfusion (P ＜0.05).There was no expression of bax in sham group.At 3 day after reperfusion,there was no significance among I/R,Cur100,Cur30 and Cur300 groups (P ＞0.05).In I/R,Cur30,Cur100 and Cur300 groups,the expression of pJNK in CA1 and CA3 regions began to increase at 2 h after reperfusion,then reached peak at 1 day and decreased,and the expression level was decreased to the normal level at 7 day.At 6 h,1 day and 3 day after reperfusion,the expression of p-JNK was higher in I/R group than in Cur300,Cur30,Cur100 and shamgroups ( P ＜ 0.05),and the intensity of expression level was Cur300 ＞ Cur30 ＞ Cur100 ＞ sham ( P ＜0.05 ).The apoptotic neurons presented mostly in CA1 region in each group.There were only a few apoptotic neurons at 2 h,the number of apoptotic neurons reached peak at 3 day,and then decreased. The number of apoptotic neurons was less at 6 h,1 day,and 3 day in Cur100 group than in I/R,Cur300 and Cur30 groups ( P ＜ 0.05 ).Conclusion Curcumin can significantly decrease the number of apoptotic neurons in hippocampus after ischemia reperfusion in SD rats probably by decreasing the expression of p-JNK and bax,and increasing the expression of bcl-2.The effect of 100 mg/kg curcumin is better than that of 30and 300 mg/kg. Key words: Curcumin; Cerebral ischemia; Apoptosis; Hippocampus