吡格列酮对脑缺血再灌注损伤大鼠的神经保护作用及其机制的研究

摘要

Objective To investigate the neuroprotection of Pioglitazone and its mechanisms in rats with cerebral ischemia reperfusion (CIR) injury. Methods Eighty SD rats were randomly divided into sham-operation group (group A) , CIR model group ( group B) , Pioglitazone group ( group C) , GW9662 + Pioglitazone group (group D) and Dimethyl sulfoxide group (group E) , with 16 rats in each group. Rats model of CIR injury were established by suture embolism, relevant medicines (normal saline in group A and group B)were intravenous injected into rats 3 d before operation respectively, one time a day for 3 d. After 24 h of reperfusion, neurological deficit score ( NDS) were performed for each group, ELISA was respectively used to detect levels of NF-KB and IFN-γ in cerebral tissue, HE staining was used to observe morphologic changes of neuron cells in ischemia region, Nissl and TUNEL staining were used to detect the number of neurons and neuron apoptosis. Then the linear correlation analysis was used to determine the association between the levels of NF-KB and IFN-γ in cerebral tissue ( group B, group C). Results Compared with group A, the NDS, the levels of NF-KB and IFN-γ, the number of neurocytes apoptosis were significantly increased and the number of neurons was significantly decreased in the other four groups ( P < 0.05 —0.01) ; compared with group C, the NDS, the levels of NF-KB and IFN-γ and the number of neurocytes apoptosis were significantly increased and the number of neurons was significantly decreased in group B, D and E ( all P < 0. 05) ; the levels of IFN-γ and NF-KB in group B and C were perfect positive correlations ( r = 0. 952, r = 0. 978, all P < 0. 001). Conclusion Pioglitazone provides significantly protection from CIR injury. It is probably through to down-regulating NF-kB levels and then to reduce the release of IFN-γ, and increase the number of neurons and inhibit the apoptosis of neurons, thus protecting the neurons.%目的 探讨吡格列酮对脑缺血再灌注(CIR)损伤大鼠的神经保护作用及其机制.方法 将80只SD大鼠随机分为假手术组(A组)、CIR模型组(B组)、吡格列酮干预组(C组)、GW9662+吡格列酮组(D组)及二甲基亚砜组(E组),每组16只.用线栓法制作CIR损伤大鼠模型,于术前3d起分别给予各组大鼠相应药物(A组和B组大鼠为生理盐水)静脉注射；均为每天1次,连续3d.在缺血再灌注24 h后给各组大鼠进行神经功能缺损评分(NDS),用ELISA法测定大鼠脑组织核因子-κB (NF-κB)及干扰素-γ(IFN-γ)水平,HE染色观察缺血区病理学改变,尼氏染色和原位末端标记染色检测神经元数及凋亡细胞数.对大鼠脑组织NF-κB与IFN-γ水平(B组,C组)的相关性作直线相关分析.结果 与A组相比,其他4组的NDS、脑组织NF-κB和IFN-γ水平、细胞凋亡数均明显升高,健存神经细胞数明显减少(P ＜0.05 ～0.01).与C组相比,B组、D组、E组的NDS、NF-κB和IFN-γ水平、细胞凋亡数均显著升高,健存神经细胞数明显减少(均P＜0.05).B组、C组大鼠脑组织NF-κB与IFN-γ水平呈正相关(r=0.952,r =0.978,均P＜0.001).结论 吡格列酮对CIR损伤有显著的神经保护作用.其可能通过下调脑组织NF-κB的表达,减少IFN-γ,的释放,使健存神经细胞增加、神经细胞凋亡减少,从而发挥神经保护作用的.