垂体腺苷环化酶激活肽对缺血再灌注脑神经元凋亡的作用

The effects of pituitary adenylate cyclase activating polypeptide on neuron apoptosis during complete cerebral ischemia reperfusion injury

目的:观察垂体腺苷环化酶激活肽(pituitaryadenylatecyclase-activatingpolypeptide,PACAP)对缺血再灌注脑神经元凋亡的防治作用。方法:利用四血管结扎法,建立老龄大鼠脑缺血再灌注模型,侧脑室注射PACAP,观察脑组织丙二醛(MDA)含量和超氧化物歧物酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,计数海马CA1区存活和凋亡神经元数目,电镜观察神经元的超微结构变化。结果:PACAP治疗后脑组织MDA含量为(1.35±0.39)nmol/mg,SOD和GSH-Px活性分别为(115±20)NU/mg、(10.3±2.0)U/mg,与缺血再灌注组有明显差异(P<0.05),海马CA1区存活和凋亡神经元数目为48.8±4.3,14.3±2.9,能促进神经元存活和减轻凋亡损伤(P<0.01),保护超微结构。结论:PACAP的保护作用可能与其降低脑组织氧自由基水平,提高抗氧化酶活性,防止神经元凋亡有关。

AIM:To explore the protective effects of pituitary adenylate cyclase activating polypeptide(PACAP) on neuron apoptosis during complete cerebral ischemia reperfusion injury.METHODS:Complete cerebral ischemia reperfusion injury models were created by the four vessle ligation method.PACAPs were infused into lateral ventricle. The malondialdehyde(MDA),superoxide dismutase (SOD), glutathione peroxidase(GSH PX), the amount of survival and apoptotic neurons were counted. The ultrastructures in hippocampal CA1 area were also observed. RESULTS:The MDA content was(1.35±0.39)nmol/mg, SOD and GSH PX activity were(115±20) NU/mg,(10.3±2.0)U/mg in rats brain after PACAP treatment, which were remarkably different from those in cerebral ischemia reperfusion group(P< 0.05). The number of survival neurons(48.8±4.3) was increased and apoptotic neurons(14.3±2.9) were reduced remarkably(P< 0.01). And ultrastrctures in CA1 area were also prevented. CONCLUSION:The protective effects of PACAP may be related to its function of reducing the reactive oxygen species and increasing antioxidant enzyme activity.