CAJ | 학술논문

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(0.65 mg/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CA1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.
목적 탐토과양화물매체증식물격활수체γ(peroxisome proliferator-activated receptor-γ,PPARγ)격동제필격렬동대뇌결혈대서해마CA1구효질섬유산성단백(glial fibrillary acidic protein,GFAP)화주기단백D1표체적영향.방법 54지Sprague-Dawley대서수궤분위가수술조、결혈재관주조화필격렬동간예조,매조18지.채용개량선전법제작대서대뇌중동맥폐새재관주모형.필격렬동간예조재모형제작전련속5d필격렬동관위(0.65 mg/kg,1차/d).재모형제작후1d、3d화7d시(매개시간점6지)처사대서취뇌.HE염색관찰해마CA1구신경원병이학변화.면역조화염색법검측해마CA1구GFAP화주기단백D1표체.결과 결혈재관주조해마CA1구신경원존활수량재결혈재관주3d화7d시균교가수술조현저감소(P균＜0.01),GFAP화주기단백D1재각개시간점표체균교가수술조현저상조(P균＜0.01).필격렬동간예조해마CA1구신경원존활수량재결혈재관주3d화7d시균교결혈재관주조현저증다(P균＜0.01),GFAP화주기단백D1재각개시간점표체균교결혈재관주조현저하조(P균＜0.01).결론 PPARγ격동제필격렬동대뇌결혈재관주대서해마CA1구신경원구유명현적보호작용,기궤제가능여억제GFAP화주기단백D1표체유관.
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 CA1 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 pioglitazone rosiglitazone gavage (0.65 mg/kg once a day) was conducted for 5 days before modeling in the pioglitazone 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 cyclin D1 in the hippocampal CA1 region.Results Compared to the sham operation group,at day 3 and 7 after ischemia/reperfusion,the number of neuronal survival in the hippocarmpal 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 after ischemia/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 PPARγagonist 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.