[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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Yang
Xiaoyan
X
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Zhang
Li
L
Jiang
Shiqin
S
Gong
Peili
P
Zeng
Fandian
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D002546:Ischemic Attack, Transient / Q000601:surgery*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D044182:Benzylisoquinolines; D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; C035934:dauricine; D045304:Cytochromes c; D020169:Caspases