缺血后适应对树鼩血栓性脑缺血时海马rCBF与AS活化偶联反应的影响及其可能机制
首发时间:2007-07-16
摘要:目的:研究树鼩局部脑缺血海马rCBF与星形胶质细胞(astrocyte,AS)活化的偶联反应,探讨缺血后适应(postconditioning,PC)对rCBF与AS表达胶质纤维酸蛋白(glial fibrillary acidic protein,GFAP)的影响及其机制。方 法:建立树鼩血栓性局部脑缺血及缺血PC模型,通过激光多普勒(laser-Doppler,LD)血流计测量脑缺血后4、8、12、24及72h海马CA1区rCBF的改变;用免疫组化法测定脑缺血上述时间海马GFAP的表达,并用图像分析系统测定其平均灰度值。于脑缺血后4h重复3次夹闭缺血侧颈总动脉实施缺血PC,并观察其对海马CA1区rCBF和AS活化以及GFAP表达的影响。结 果:树鼩脑缺血后4h海马CA1区GFAP阳性细胞数增多,AS表达GFAP增强,24h可见AS胀亡;72h海马CA1区AS表达GFAP达高峰(120±2.08,P<0.01)。脑缺血时海马rCBF逐渐降低,以24h的改变最显著(为2.55±0.28PU,P<0.01);72h时海马rCBF略有增加,为9.84±1.22 PU。实施缺血PC后,海马CA1区rCBF逐渐增加,72h最显著(为18.74±1.6 PU,P<0.01);此时海马GFAP表达进一步增强(111±1.29,P<0.01),但AS胀亡的病理改变基本消失。结 论:树鼩脑缺血时海马CA1区rCBF减少的程度与GFAP表达增加具有偶联反应;多次、短暂的闭塞动物的颈动脉可延长脑缺血治疗的“时间窗”;缺血PC的脑保护机制可能与增加海马rCBF,适当活化AS及改善海马微环境有关。
关键词: 光化学 脑缺血 缺血后适应 局部脑血流 星形胶质细胞活化 胀亡 偶联反应 树鼩
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Effects of ischemic postconditioning on hippocampus rCBF and AS activation coupling response and possible mechanisms after thrombotic cerebral ischemia in tree shrews
Abstract:AIM: To study the coupling response of the regional cerebral blood flow (rCBF) and astrocyte (AS) activation coupling response in hippocampus CA1 area and to explore the possible mechanism and the effects of ischemic prostconditioning on rCBF and glial fibrillary acidic protein (GFAP) expression during focal cerebral thrombosis. METHODS: The thrombotic focal cerebral ischemia was induced by photochemical reaction in tree shrews, and ischemic postconditioning was established by cliped ipsilateral carotid of the animal at 4 hours after cerebral ischemia. The rCBF and GFAP expression in hippocampus CA1 area were detected, respectively, by laser-Doppler(LD) fowmeter and immunohistochemistry. RESULTS: The number of GFAP positive cells were increased markedly and GFAP expression enhanced(P<0.01), AS oncosis were apparent 24 hours after cerebral ischemia. Postconditioning may increase hippocampus rCBF from 2.55±0.28 PU to 10.42±3.75 PU (P<0.05) at 24 hours and from 9.84±1.22 PU to 18.74±1.6 PU ( P<0.05) at 72 hours after the cerebral ischemia, and AS oncosis were inhibited markedly. CONCLUSION: The degrees rCBF reduction and AS activation in hippocampus CA1 shown a coupling response after focal cerebral thrombosis. Multiple, short, regional carotid occlusions may prolong “time window” of therapeutic cerebral ischemia, and the protection mechanism of ischemic prostconditioning may associated with the increase of rCBF, appropriate activation of AS and improvement of hippocampus microenvironment.
Keywords: Photochemistry Cerebral ischemia Prostconditioning Regional cerebral blood flow Astrocyte activation Coupling response Oncosis Tree shrew
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缺血后适应对树鼩血栓性脑缺血时海马rCBF与AS活化偶联反应的影响及其可能机制
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