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神经调节素对大鼠脑缺血再灌注损伤细胞凋亡和STAT3及GFAP表达的影响
INFLUENCE OF NEUREGULIN ON NEURONAL APOPTOSIS AND EXPRESSIONS OF STAT3 AND GFAP FOLLOWING CEREBRAL ISCHEMIC REPERFUSION INJURY IN RATS
【摘要】 目的探讨神经调节素-1β(NRG-1β)对大鼠脑缺血再灌注损伤细胞凋亡、信号转导和转录激活因子3(STAT3)及胶质纤维酸性蛋白(GFAP)表达的影响。方法成年雄性Wistar大鼠,用线拴法经颈外-颈内动脉插线建立大脑中动脉闭塞再灌注(MCAO/R)动物模型,经颈内动脉单剂量注射1.5NRG-1β5μl干预治疗。荧光DendEndTUNEL法检测神经细胞凋亡;免疫组织化学和免疫荧光染色检测脑组织STAT3和GFAP表达。结果脑缺血再灌注损伤可诱导脑组织细胞凋亡和STAT3及GFAP表达。对照组随缺血时间延长,皮质、纹状体和海马区细胞凋亡逐渐增多,STAT3和GFAP表达逐渐增强。治疗组在缺血不同时间点细胞凋亡较对照组相应脑区显著减少(P<0.05),STAT3和GFAP表达水平较对照组相应脑区显著增强(P<0.05)。结论NRG-1β可能通过激活细胞JAK/STAT信号传导途径,促进星形细胞胶质化,启动神经细胞抗凋亡机制,对缺血性脑损伤起保护作用。
【Abstract】 Objective To observe the influence of neuregulin-1β(NRG-1β) on neuronal apoptosis and the expressions of signal transducer and activator of transcription(STAT3) and glial fiberillary acidic protein(GFAP) following cerebral ischemia/reperfusion in rats.Methods The animal models of middle cerebral artery occlusion/reperfusion(MCAO/R) was established by the intralumianl filament method from left external-internal carotid artery in adult healthy male Wistar rats.The rat models were treated by injecting 1.5% NRG-1β 5μl from internal carotid artery.The neuronal apoptosis was detected by DendEnd fluorometric TUNEL assay,and the expressions of STAT3 and GFAP were determined by immunohistochemical and immumofluorescent assays.Results The cerebral ischemia/reperfusion injury could induce neuronal apoptosis and the expressions of STAT3 and GFAP in brain tissue.In control group,the number of neuronal apoptosis increased gradually and the STAT3 and GFAP were expressed highly along ischemia times in the cortex,striatum and hippocampus areas.After treatment with NRG-1β,the number of neuronal apoptosis reduced and the expression level of STAT3 and GFAP increased when compared to those in the control group at different ischemia times and corresponding areas(P<0.05).Conclusion NRG-1β might play a neuroprotective role in cerebral iscehemia injury by activating JAK/STAT signal transduction pathway,thus promoting astrogliosis and regulating the anti-appoptosis mechanism of neural cells.
【Key words】 Neuregulins; Cerebral ischemia; Reperfusion injury; Neuronal apoptosis; STAT3; GFAP; Immumofluorescent assay; Rat;
- 【文献出处】 解剖学报 ,Acta Anatomica Sinica , 编辑部邮箱 ,2008年06期
- 【分类号】R743
- 【被引频次】11
- 【下载频次】477