[Effect of dauricine on apoptosis and expression of apoptogenic protein after transient focal cerebral ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the effect of dauricine on the apoptosis of neuronal cells and the expression of apoptosis-related proteins in the brain penumbra of rats induced by transient focal cerebral ischemia-reperfusion injury.

METHOD: Male SD rats were randomly divided into five groups: sham group (Sham), model group (Model), and Dauricine groups of low, middle and high doses. To make the transient focal cerebral ischemia-reperfusion injury model, the middle cerebral artery on the right side of rat was occluded by inserting a nylon suture through the internal carotid artery for 1 h, followed by reperfusion for 24 h after withdrawing the suture. Dauricine groups, different doses of Dauricine (2.5, 5, 10 mg x kg(-1) as low, middle and high dose respectively) were administered intraperitoneally at the beginning of the cerebral ischemia, and at 11 h and 23 h after reperfusion. At the same time, Sham group and Model group was administered saline as controls. Brain samples of rats were treated with paraformaldehyde perfusion fixation 24 h after blood reperfusion and then collected for making pathological sections. Apoptotic changes of neuronal cells in the brain penumbra of rat were evaluated in situ by terminal deoxyribonucleotidyl transferasemediated dUTP-digoxigenin nick end-labelling (TUNEL). Cytochrome C (Cyt-C) release and the expression of caspase -3 and caspase -9 proteins of the ischemic-reperfusion brain tissue were determined by immunohistochemistry assay.

RESULT: TUNEL-positive cells in groups of middle and high doses of dauricine (18.9 +/- 2.02 and 15.9 +/- 2.9 cells/mm2 respectively) decreased significantly compared with model group (25.5 +/- 3.3 cells/mm2, P<0.05). Cyt-C release and the expression of caspase-3 and caspase-9 proteins in groups of middle and high doses of dauricine were also inhibited compared with Model group (P<0.01).

CONCLUSION: The mechanism of the neuroprotective effect of dauricine after cerebral ischemia-reperfusion injury may parly, related with an inhibition of neuronal cells apoptosis in the penumbra.