Effect of cilostazol pretreatment on poly (ADP-ribose) polymerase/apoptosis-inducing factor pathway induced nerve cell apoptosis in rats after focal cerebral ischemia/reperfusion
10.3760/cma.j.issn.1671-8925.2013.01.004
- VernacularTitle:西洛他唑对大鼠脑缺血再灌注损伤后PARP/AIF介导的细胞凋亡途径的影响
- Author:
Xiao-Hong BA
1
;
Ying LIU
Author Information
1. 辽宁医学院附属第一医院神经科
- Keywords:
Cerebral ischemia reperfusion;
Poly (ADP-ribose) polymerase;
Apoptosis-inducing factor;
Cilostazol;
Cell apoptosis
- From:
Chinese Journal of Neuromedicine
2013;12(1):13-18
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the expressions of poly(ADP-ribose) polymerase (PARP) and apoptosis-inducing factor (AIF) in the hippocampal CA1 region of rats after focal cerebral ischemia reperfusion injury,and elucidate the neuroprotective effect ofcilostazol pretreatment through PARP/AIF pathway.Methods One hundred and thirty-five male SD rats were randomly divided into three groups (n=45) for experiments:sham-operated group,ischemia/reperfusion (I/R) vehicle group and cilostazol pretreatment group.Embolization thread was inserted into all rats except those in the sham-operated group for 2 hours to establish middle cerebral artery occlusion models; and then,reperfusion for 6,24,72 hours was performed,and rats of each group were sub-divided into three groups according to reperfusion times (n=l 5).Cilostazol pretreatment group was given cilostazol (30 mg/kg,twice orally) before surgery.The apoptosis cells of the hippocampus were detected by Terminal deoxynucleotidyl Transferasemediated dUTP nick end-labeling (TUNEL).Western blotting was used to test the dynamic changes of AIF and polyadenosine diphosphate ribose (PAR) levels at different times.The mRNA expression of AIF was assessed by real time-PCR.Results There appeared subsequent translocation of AIF after focal cerebral ischemia reperfusion injury in rats.As compared with those in the sham-operated group,the apoptotic cells statistically increased; AIF and PAR contents and AIF mRNA expression significantly increased in the I/R vehicle group reaching its peak level at 24 h ofreperfusion (P<0.05).As compared with of the I/R model subgroups,the cilostazol pretreatment subgroups had significantly decreased AIF and PAR contents,AIF mRNA expression and number of apoptosis cells (P<0.05); 24 h of reperfusion subgroup had the most obvious effect (P<0.05).Conclusion Cilostazol pretreatment in rats after ischemia-reperfusion injury has certain neroprotective effect,whose resistance roles in nerve cell apoptosis may be implemented by inhibiting excessive PARP activation and AIF translocation caused by cerebral ischemia injury.