新型AMPA受体拮抗剂对脑梗死再灌注损伤的保护作用

Protective effects of new type of AMPA receptor antagonist on cerebral infarction reperfusion injury

目的探讨新型AMPA受体拮抗剂他仑帕奈(Talampanel,TAL)对缺血性脑卒中的脑保护作用及其可能机制。方法实验大鼠分为假手术组(Sham组)、模型组(MCAO组)、TAL组,根据TAL组给药时间的不同,分TAL0 h、TAL1 h、TAL3 h、TAL5 h 4个亚组。利用线栓法建立大脑右侧中动脉脑梗死模型。Z-Longa评分; TTC染色比较各组大鼠脑梗死体积; HE染色观察海马CA_1区神经元的形态变化;免疫组织化学方法观察脑梗死周围区caspase-3的表达及梗死皮质区神经元数量。结果与MCAO组相比,TAL各组海马CA_1脑水肿和神经元病理损害程度明显减轻,神经功能损伤评分及脑梗死体积明显降低(P <0. 05),梗死周围区caspase-3阳性细胞数明显减小(P <0. 05),梗死皮质区存活神经元数量明显增加(P <0. 05),而TAL5 h组较TAL0 h、TAL1 h、TAL3 h给药组相比,脑保护作用减弱(P <0. 05)。结论他仑帕奈可通过减少缺血再灌注大鼠神经功能损伤评分,缩小脑梗死体积,减少caspase-3阳性细胞表达,对脑缺血再灌注损伤具有很好的保护作用,对脑保护作用具有一定的时间依赖性,随着时间延长,脑保护作用会减弱。

Objective To investigate the protective effect of Talampanel(TAL),a novel AMPA receptor antagonist,on ischemic stroke and its possible mechanism.Methods The experimental rats were divided into four groups:the sham operation group(group Sham),the model group(MCAO group)and the TAL group.According to the different time of the administration of the TAL group,the four subgroups were divided into TAL0 h,TAL1 h,TAL3 h,TAL5 h.The right middle cerebral artery infarction model was established by thread embolism.Z-Longa score;TTC staining was used to compare the volume of cerebral infarction in rats of each group;HE staining was used to observe the morphological changes of hippocampal neurons in CA 1 region;the expression of caspase-3 in the surrounding area of cerebral infarction and the number of neurons in infarct cortex were observed by immunohistochemistry.Results Compared with the MCAO group,the degree of cerebral edema and neuron pathological damage in hippocampus of TAL was obviously reduced,the score of nerve function injury and the volume of cerebral infarction decreased significantly(P<0.05),the number of caspase-3 positive cells in the surrounding area decreased significantly(P<0.05),the number of surviving nerve elements in the infarct cortex increased significantly(P<0.05),and TAL5 h group was more than TAL0 h and T.The protective effect of AL1 h and TAL3 h decreased in the drug delivery group(P<0.05).Conclusion By reducing the nerve function injury score of ischemia reperfusion rats,it can reduce the volume of cerebral infarction and reduce the expression of caspase-3 positive cells.It has a good protective effect on cerebral ischemia reperfusion injury.It has a certain time dependence on the brain protection,and the protective effect of brain will be weakened with time.