前列腺素E受体1在缺氧性神经细胞死亡中的作用

Role of prostaglandin E_2 receptor 1 in neuronal cell death induced by hypoxia on rat cortical neurocytes

目的:探讨前列腺素E受体1(EP1)在缺氧性神经细胞死亡中的作用。方法:采用原代培养的大鼠出生24h内的大鼠子鼠皮质神经细胞,给予缺氧再给氧处理,用噻唑蓝比色法(MTT)测定神经细胞生存率,流式细胞技术测定细胞凋亡率,用Western印迹法检测caspase-3蛋白质的表达。结果:EP1激动剂17-pt能明显降低缺氧再给氧后神经细胞的生存率,细胞生存率呈浓度依赖性,17-pt预处理组与单纯缺氧再给氧组相比,17-pt能明显增加由于缺氧而引起的细胞死亡率,细胞凋亡率增高,caspase-3蛋白质表达量增加(P<0.05)。结论:EP1参与了缺氧缺血后神经细胞死亡的病理过程,有可能成为缺血性中风治疗的新分子靶点。

AIM：To observe the effects of prostaglandin E2 receptor1 （EP1） in neuronal cell death induced by hypoxia/reoxygenation and ischemia/reperfusion. METHODS：The cortical neurocytes of neonatal Wistar rats were cultured for 12 days and exposed to hypoxia/re-oxygenation to establish a hypoxia/re-oxygenation model. Another set of cultured primary neonatal cortical neurocytes of rats were pretreated with 17-pt （an antagonist of EP1）,then underwent hypoxia for 3 h,re-oxygenated for 21 h. MTT reagent was added 1 h before measuring the cell viability. Neuron apoptosis was determined by flow cytometry. The protein expression was examined by Western blotting. RESULTS：Compared to the control cells （only underwent hypoxia /re -oxygenation and without any pretreatment）,the neurons pretreated with 17-pt and then underwent hypoxia/re-oxygenation showed significantly lower survival rate （P 0. 05） and increased expression level of caspase -3 and neuron apoptosis. CONCLUSION：EP1 is involved in the pathogenesis of neuron death induced by hypoxia/ischemia and may be a new target for treating ischemic stroke.