长春西汀通过调控核因子-κBp65、过氧化物酶体增殖物激活受体γ和环氧合酶-2表达减轻大鼠脑缺血灌注损伤  

Vmpocetine ageviates cerebral ischemia-repedusion injury ht rats by regulation of the expressions of nuclear factor κB p65, peroxisome prolerator-activated receptor γ, and cyclooxygenase-2

作　　者：邱小波[1,3] 王健[1] 何兰英[1] 罗勇[2] 

机构地区：[1]成都市第二人民医院神经内一科,610017 [2]重庆医科大学附属第一医院神经内科,重庆市神经病学重点实验室,400016 [3]成都市第二人民医院医务科,610017

出　　处：《国际脑血管病杂志》2015年第7期517-521,共5页International Journal of Cerebrovascular Diseases

摘　　要：目的通过观察长春西汀注射液对局灶性脑缺血再灌注大鼠缺血皮质过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor γ，PPAR-γ）、核因子（nuclearfactor，NF）-κBp65、环氧合酶-2（cyclooxygenase-2，COX-2）表达以及梗死体积的影响探讨其神经保护机制。方法应用线栓法建立大鼠局灶性脑缺血再灌注模型，随机分为假手术组、缺血再灌注组和长春西汀组，再根据再灌注时间分为7d和14d亚组，每组6只。应用蛋白质印迹法检测缺血皮质PPA脚和NF-κBP65表达水平，应用逆转录聚合酶链反应检测COX-2mRNA表达水平，氯化三苯基四氮唑染色法检测脑梗死体积。结果蛋白质印迹法显示，脑缺血再灌注后7d和14d时，脑缺血再灌注组PPARγ和NF—κBp65（P均〈0．001）蛋白表达水平均显著高于假手术组，长春西汀组PPAIh（P均〈0．05）表达水平显著高于脑缺血再灌注组，但NF—κBp65（P均〈0．05）表达水平显著低于脑缺血再灌注组。逆转录聚合酶链反应显示，脑缺血再灌注后7d和14d时，COX-2mRNA表达水平较假手术组显著上调（P均〈0．001），长春西汀组COX-2mRNA表达水平较脑缺血再灌注组显著下调（P均〈0．05）。脑缺血再灌注后7d[（134．308±9．954）mm。对（185．543±9．100）mm0；q=10．659，P〈0．0011和14d1137．865±9．094）mm2对183．210±4．368）mm2；q=11．166，P〈0．001]长春西汀组梗死体积均显著小于脑缺血再灌注组。结论长春西汀能显著缩小局灶性脑缺血再灌注梗死体积，其机制可能为上调PAARγ以及下调NF-κBp65和COX-2表达有关。Objective To investigate neuroprotective mechanisms of vinpocetine by observing the effects of vinpocetine injection on the expressions of peroxisome proliferators-activated receptor -γ（PPAR-γ）, nuclear factor （NF）-κB p65, cyclooxygenase-2 （COX-2） in the ischemic cortex, and infarct volume after focal cerebral ischemia-reperfusion in rats. Methods A focal cerebral ischemia-reperfusion injury model was induced by suture method. The rats were randomly divided into a normal control, a cerebral ischemia- reperfusion and a vinpocetine groups. They were also divided into either a day 7 subgroup or a day 14 subgroup （n = 6 in each subgroup） according to the reperfusion time. Western blot was used to detect the expression levels of PPAR-γand NF-kB P65 in the ischemic cortex. Triphenyl tetrazolium staining was used to detect the volume of cerebral infarction. Results Western blot showed that at day 7 and 14 after cerebral ischemia-reperfusion, expression levels of PPARγ （all P 〈 0.001 ） and NF-κB p65 （all P 〈 0.001 ） in the cerebral ischemia-reperfusion group were significantly higher than those in the sham operation group, the expression levels of PPARγ （all P 〈0. 05） in the vinpocetine group were significantly higher than those in the cerebral ischemia-reperfusion group, but the expression levels of NF-κB p65 （all P 〈0. 05） were significantly lower than those in the cerebral ischemia-reperfusion group. Reverse transcription polymerase chain reaction showed that COX-2 mRNA expression levels were upregulated significantly at day 7 and 14 after cerebral ischemia-reperfusion compared with the sham operation group （all P 〈 0. 001 ）, the expression levels of COX-2 mRNA in the vinpocetine group were significantly downregulated compared with the cerebral lschemia-reperfusion group （all P〈 0. 05）. The infarct volumes at day 7 （134. 308 ± 9.954 mm3 vs. 185. 543±9.100 mm3; q= 10. 659, P〈0.001） and at day 14 （137. 865±9.094mm3 vs. 183. 210± 4, 368 ram3; q= 11.

关 键 词：脑缺血 再灌注损伤 长春花生物碱类 PAARγ NF—κB 环氧合酶2 神经保护药 大鼠 

分 类 号：R743[医药卫生—神经病学与精神病学]