GDNF对大鼠脑缺血/再灌注损伤的治疗时间窗与caspase-3表达的关系

Relationship between therapeutic time window of GDNF for cerebral ischemia/reperfusion injury of rats and expression of caspase-3

目的 :探讨胶质细胞源性神经营养因子 (GDNF)对大鼠脑缺血再灌注损伤的治疗时间窗与半胱天冬酶 3(caspase 3)蛋白表达的关系。 方法 :建立大鼠大脑中动脉闭塞 2h模型 ,再灌注 0 ,1,3h分别给予GDNF ,观察再灌注 10h及 2 2h缺血半暗带caspase 3蛋白表达。TTC染色测定梗死灶体积。结果 :1h给药组脑梗死灶体积较 0h给药组增大 ,caspase 3蛋白表达增加(P<0 .0 5 )。3h给药组脑梗死灶体积较 1h给药组增大 ,caspase 3蛋白表达增加 (P <0 .0 5 )。0h及 1h给药组再灌注 2 2h较 10hcaspase 3蛋白表达减少 ,3h给药组再灌注 2 2h较 10hcaspase 3蛋白表达增加(P<0 .0 5 )。结论 :GDNF对缺血半暗带caspase 3蛋白表达与治疗时间窗有关 ,GDNF可通过减少caspase 3的表达减少脑缺血 /再灌注损伤细胞凋亡的发生。

Objective: To discuss the relationship between the therapeutic time window of glial cell line-derived neurotrophic factor (GDNF) for cerebral ischemia/reperfusion injury of rats and expression of cysteinyl asparate-specific proteinase-3 (caspase-3) protein. Methods: Rat model of transient focal cerebral ischemia was made by 2-hour occlusion of the midle cerebral artery.The GDNF was administrated 0,1,3 hours after reperfusion. We observed the expression of caspase-3 protein 10 and 22 hours after reperfusion. Infarct size was calculated by using TTC staining method. Results: Infarct volume and expression of caspase-3 protein in 1-hour group were greater than those in 0-hour group (P<0.05). Those in 3-hour group were greater than those in 1-hour group (P<0.05). The expression of caspase-3 protein 22 hours after reperfusion was less than that 10 hours after reperfusion in 0-and 1-hour group,However,the expression was greter in 3-hour group 22 hours after reperfusion than that 10 hours reperfusion (P<0.05). Conclusion: The effect of GDNF on the expression of caspase-3 in penumbra is relatedt with the therapeutic time window. The GDNF can reduce the incidence of neuronal apoptosis during the cerebral ischemia reperfusion injury by reducing the expression of caspase-3 protein.