摘要
目的探讨过氧化物酶体增殖物激活受体γ（peroxisome proliferator—activated receptor-γ，PPARγ）激动剂吡格列酮对脑缺血大鼠海马CA1区胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）和周期蛋白D1表达的影响。方法54只Sprague—Dawley大鼠随机分为假手术组、缺血再灌注组和吡格列酮干预组，每组18只。采用改良线栓法制作大鼠大脑中动脉闭塞再灌注模型。吡格列酮干预组在模型制作前连续5d吡格列酮灌胃（0．65mg/kg，1次／d）。在模型制作后1d、3d和7d时（每个时间点6只）处死大鼠取脑。HE染色观察海马CA1区神经元病理学变化。免疫组化染色法检测海马CA1区GFAP和周期蛋白D1表达。结果缺血再灌注组海马CAI区神经元存活数量在缺血再灌注3d和7d时均较假手术组显著减少（P均〈0．01），GFAP和周期蛋白D1在各个时间点表达均较假手术组显著上调（P均〈0．01）。吡格列酮干预组海马CA1区神经元存活数量在缺血再灌注3d和7d时均较缺血再灌注组显著增多（P均〈0．01），GFAP和周期蛋白D1在各个时间点表达均较缺血再灌注组显著下调（P均〈0．01）。结论PPARγ激动剂吡格列酮对脑缺血再灌注大鼠海马CA1区神经元具有明显的保护作用，其机制可能与抑制GFAP和周期蛋白D1表达有关。
Objective To investigate the effects of peroxisome proliferators-activated receptorγ（PPARγ） agonist pioglitazone on the expressions of glial fibrillary acidic protein （GFAP） and cyclin D1 in the hippocampal CAI region after cerebral ischemia in rats. Methods Fifty-four Sprague-Dawley rats were randomly divided into 3 groups： sham operation group, ischemia/reperfusion group, and pioglitazone intervention group （18 in each group）. A rat middle cerebral artery occlusion and reperfusion model was induced by the modified suture method. Continuous piogiitazone rosiglitazone gavage （0. 65 mg/kg, once a day） was conducted for 5 days before modeling in the piogtitazone intervention group. At day 1, 3, and 7 after modeling, the rats （6 at each time point） were sacrificed and their brains were removed. HE staining was used to detecte the pathological changes of neurons in the hippocampal CA1 region, Immunohistochemical staining was use to detect the expressions of GFAP and cyclirl D1 in the hippocarnpal CAI region. Results Compared to the sham operation group, at day 3 and 7 after ischemia/reperfusion, the number of neuronal survival in the hippocampal CA1 region in the ischemia/reperfusion group was significantly reduced （all P 〈 0. 01）. The expressions of GFAP and Cyclin D1 at all time points were significantly upregulated （all P 〈 0.01 ）. At day 3 and 7 afterischemia/reperfusion, the numbers of neuronal survival in the hippocampal CA1 region in the pioglitazone intervention group were significantly increased （all P 〈0, 01）. Compared to the ischemia/reperfusion group, the expressions of GFAP and Cyclin D1 at all time points were significantly down-regulated （all P 〈 0. 01 ）. Conclusions PPAR-γ agonist pioglitazone has a significant protective effect on neuron in the hippocampal CA1 region after cerebral ischemia/reperfusion in rats. Its mechanism may be associated with inhibiting GFAP and cyclin D1 expressions.
出处
《国际脑血管病杂志》
北大核心
2012年第12期924-930,共7页
International Journal of Cerebrovascular Diseases
基金
广西科学自然基金（桂科自：0832133）
