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

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2 h模型,再灌注0,1,3 h分别给予GDNF,观察再灌注10 h及22 h缺血半暗带caspase-3蛋白表达.TTC染色测定梗死灶体积.结果:1 h给药组脑梗死灶体积较0 h给药组增大,caspase-3蛋白表达增加(P＜0.05).3 h给药组脑梗死灶体积较1 h给药组增大,caspase-3蛋白表达增加(P＜0.05).0 h及1 h给药组再灌注22 h较10 h caspase-3蛋白表达减少,3 h给药组再灌注22 h较10 hcaspase-3蛋白表达增加(P＜0.05).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.

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

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.