大鼠短暂性全脑缺血后STAT3表达与神经原凋亡的关系

Relationship between STAT3 expression and neuron apoptosis following transient global cerebral ischemia in rats

目的 探讨短暂性全脑缺血／再灌注（I／R）大鼠海马CAI区信号转导和转录激活子-3（STAT3）表达与迟发性神经元凋亡的关系。方法 30只健康雄性SD大鼠，随机分为假手术组（n=5）和全脑I／R后4、24、48、72、96h组（n=5）。双侧颈总动脉阻断＋全身低血压法建立大鼠短暂性全脑缺血模型；运用Nissl和TUNEL染色观察海马CA1区神经元存活数和凋亡细胞数；免疫组化法检测STAT3蛋白在全脑I／R后的表达。结果 全脑I／R后24h，海马CAI区STAT3阳性细胞数显著增多，72h达峰值，至96h开始下降。TUNEL染色显示，在I／R后24h即出现少量凋亡细胞，48～72h显著增多；STAT3蛋白高表达与神经元凋亡两者的部位和时间段基本一致。结论 STAT3蛋白表达增强可能介导缺血性脑损伤的信号转导过程，其在脑缺血损伤神经元凋亡过程中起关键作用。

Objective To investigate the relationship between signal transducers and activators of transcription-3 （STAT3） protein expression and delayed neuronal apoptosis. Methods Thirty Sprague-Dawlay rats were divided randomly into six groups （n = 5 in each group）： sham, 4, 24, 48, 72 and 96 h after ischemia-reperfusion （I/R）. Transient global ischemia was induced by bilateral common carotid artery （CCA） occlusion combined with hypotension. Nissl staining and terminal deoxynucleotidyl transferase （TdT）-mediated dUTP nick end-labeling （TUNEL） were used to count the numbers of alive neurons and apoptosis in hippocampus CAI region of rats. Immunohistochemistry with STAT3 protein polyclonal antibody was used to explore the varieties of STAT3 protein expressions after global cerebral ischemia. Results The STAT3 expressing ceils increased significantly at 24 h, and the peak appeared at 72 h, and tended to decrease at 96 h after global cerebral ischemia. There were a few apoptosis at 24 h, but increased significantly at 48 - 72 h after global cerebral isehemia. The time and space phase pattern of STAT3 protein was consistent with that of cell apoptosis. Conclusion The expressions of STAT3 increased might indicate the transmission course in ischemic nerve cell signal, and play a key role in neuron apoptosis of ischemic brain injury.