【作者】 李凡；

【导师】 李树清；

【作者基本信息】 昆明医学院 ， 病理生理学， 2003， 硕士

【摘要】 目的：在体观察脑缺血不同部位AS表达GFAP的消长改变及GB的防治效应；体外研究IL-8对AS及神经元的影响。从而阐明缺血后AS表达GFAP与IL-8及神经元的相互关系；通过观察血小板活化因子PAF受体拮抗剂GB对GFAP表达的影响，探讨GB对GFAP表达影响的机制。方法：建立光化学诱导树鼩脑缺血模型，用免疫组化法测定脑缺血不同时间，以及给予GB后，半暗区、远隔区及对侧皮层GFAP的表达，并用图像分析系统测定其平均灰度值。在体外进行AS及神经元培养，并与不同浓度IL-8分别作用4、24及72h，用MTT法和免疫组化法测定神经元存活力及AS表达GFAP的平均灰度值并计数阳性细胞数量。结果：缺血后24h半暗区AS表达GFAP达高峰(P＜0.01)，同时AS的形态发生显著改变；72h仍维持较高水平，而AS形态改变有所缓解；远隔区及对侧皮层AS于72h时表达GFAP增多(P＜0.05)；光化学反应6h给予GB后，AS表达GFAP减少。在培养的神经元和AS中加入不同浓度IL-8后，神经元数量及其形态及AS表达GFAP无明显改变，但AS数目增多；中浓度组作用72h后AS数量显著增多(P＜0.01)，而高浓度组作用24h即可见到AS数量显著增多(P＜0.01)。结论：脑缺血后24hAS表达GFAP增多具有改善微环境的作用，但由于此时缺血性损伤严重且AS功能障碍，因此神经元受损严重。脑缺血后72hAS表达GFAP仍高同时脑组织中IL-8水平升高，并伴随受损神经元修复；说明GFAP表达及IL-8可能在神经元的抗损伤中具有作用。细胞培养结果显示IL-8对神经元无损伤作用但能使AS增殖，提示脑缺血后IL-8水平升高可通过与AS作用而具有脑保护效应。脑缺血后神经元受损是引起AS表达G队P的主要原因:GB通过拮抗队F的作用保护神经元从而使AS表达GFAP减少。远隔区及对侧区G队P表达是脑缺血后扩布性抑制的一种特殊表现，半暗区与这两个区域G队P表达的机制存在差异。更多还原

【Abstract】 Objective: To observe the change of GFAP expression in astrocytes and the effect of platelet- activating factor receptor antagonist ginkgolide B on GFAP expression during thrombotic cerebral ischemia in tree shrews. In addtion, we also investigate the relationship between IL-8 and neuronal viability and GFAP expression in astrocytes under cultured conddition.Methods: The focal thrombotic cerebral ischemia was induced by photochemical reaction in tree shrews. The absorbance of GFAP expression in astrocytes was detected by immunohistochemistry in different times after foci cerebral ischemia . After treating cultured cells with IL-8, the previous method and MTT method was used respectively to observe GFAP expression in astrocytes or neuronal viability.ResultstGFAP expression increased significantly(P<0.01) at 24h within astrocytes of penumbra and keeping high at 72h, whereas GFAP expression increased(P<0.05) at 72h within the distant of infarct and contralateral cortex after cerebral ischemia. GFAP expression decreased when the animals were given GB at 6h after thrombotic cerebral ischemia . After adding IL-8 into cultured cells, the neuronal viability and GFAP expression in astrocytes had nochange,but the number of GFAP(+) cells were increased marktly in dose- and time- dependent. Conclusions:GFAP which expression in astrocytes could ameliorate the microenvironment. But astrocytes dysfuntion and ischemic injury very sever so neuronal was damaged at 24h after local cerebral ischemia.The morphological change alleviated and GFAP expression keeping high in astrocytes at 72h after cerebral ischemia. The results of cell culture show that IL-8 would increase the number of astrocytes and do not scathe neurons.Present study suggested that the interaction between IL-8 and astrocytes could benefit neuroals after local cerebral ischemia. Neuroal necrosis would result in GFAP expression in astrocytes after local cerebral ischemia and GB could protect neurons by antagonizing PAF receptor and inhibit GFAP expression.There is different meshnism of GFAP expression between distant of infarct or contralateral cortex and penumbra after cerebral ischemia.更多还原