吡格列酮作为PPARγ特异性激动剂,目前在临床主要用于治疗2型糖尿病。国内有研究报道,吡格列酮促进PPARγ mRNA和蛋白的表达,增强其对脑缺血再灌注损伤的神经保护作用,并且与剂量成正比[10]。本实验发现经吡格列酮预处理后的家兔神经功能缺损较模型组明显改善,缺血半暗带的顶叶皮质中细胞凋亡数量明显减少。由此我们认为吡格列酮可通过减少细胞凋亡而达到神经保护的作用;若事先静脉注射GW9662[11]后再给予吡格列酮,则可逆转吡格列酮的上述保护作用;同样,单独行DMSO预处理后的大鼠在相关方面未得到明显的改善。
除此之外,从脑组织病理形态学比较来看,模型组家兔脑组织变性坏死的细胞明显高于其余四组且主要分布于缺血半暗带的顶叶皮质,主要表现为神经细胞坏死,表明再灌注后缺血半暗带发生了明显的细胞变性坏死反应,符合缺血缺氧性病理变化;而经吡格列酮预处理组家兔脑组织则以神经细胞肿胀为主,表明吡格列酮具有抗细胞坏死作用,在一定程度上挽救了受损的神经细胞,对缺血再灌注脑损伤起到一定的保护作用;而预先给予GW9662后再行吡格列酮预处理及单独行DMSO预处理的家兔脑组织病理形态学方面均无明显改善,提示吡格列酮具有阻止或延缓神经细胞坏死,对保护缺血再灌注后神经细胞损伤具有积极意义,而GW9662则可逆转吡格列酮抗细胞坏死的效应。
由此可见,吡格列酮可通过减轻家兔缺血再灌注后的损伤,从而很好地减少细胞凋亡,为该药在缺血性脑血管疾病的临床使用提供一定的理论依据。
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