Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats
Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats
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氟比洛芬酯通过激活大鼠局灶性脑缺血后脑过氧化物酶体增殖物激活受体γ促进神经保护
DOI：
10.3760/cma.j.issn.0366-6999.2012.20.022
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发表时间：
2012-10-20
影响因子：
6.1
通讯作者：
Wang Chen
中科院分区：
文献类型：
--
作者：
Liu Jun-le;Jin Jian-wen;Wang Chen
背景我们以前的研究表明，环氧合酶抑制剂氟比洛芬酯（FA）是一种很有前途的治疗大鼠脑缺血的药物。本研究旨在探讨FA是否通过激活过氧化物酶体增殖物激活受体-γ来促进神经保护作用方法雄性SD大鼠48只，随机分为6组，每组10只（每组8只）：缺血再灌注（I/R）组仅行短暂性大脑中动脉闭塞（tMCAO）120 min; I/R +FA组动物给予FA I/R+FA+ GW 9662组的动物在tMCAO 120分钟后立即通过尾静脉给予GW 9662（10 mg/kg）;（一种PPAR-gamma抑制剂，1 mg/kg），在脑缺血发作前30分钟腹腔注射，I/R+ GW 9662组在缺血前30 min腹腔注射GW 9662（1 mg/kg）; I/R+DMSO组动物在脑缺血发作前30分钟腹腔内给予3%DMSO（载体GW 9662，1 ml/kg）;假手术组动物除了插入尼龙丝外经历相同的手术。再灌注72 h后行神经功能缺损评分（NDS），用氯化三苯基四氮唑（TTC）10 g/L染色法测定脑梗死体积百分比（MBIVP）再灌注后72 h，I/R组（12.0（10.0-15.0））、I/R+FA+ GW 9662组（10.0（8.0-12.0））、I/R+FA+DMSO组（12.0（9.0-14.0））与I/R组（7.5（6.0-10.0））比较，差异有统计学意义（P < 0.05）。I/R+FA组NDS（12.0（10.0-15.0））与I/R+FA+ GW 9662组NDS（10.0（8.0-12.0））有显著差异。I/R组中的MBIVP（45.82 ± 8.83）%显著高于I/R+FA组（（23.52 ± 9.90）%），I/R+FA+ GW 9662组（（33.17 ± 7.15）%）; I/R+FA组中的MBIVP（23.52 ± 9.90）%，显著小于I/R+FA+ GW 9662组结论FA对大鼠tMCAO具有神经保护作用，选择性PPAR-gamma拮抗剂GW 9662可减弱FA的保护作用。FA可通过或部分通过激活PPAR-gamma促进大鼠局灶性脑缺血后的神经保护作用。中华医学杂志2012;125（20）：3719-3724
Background Our previous papers indicate that flurbiprofen axetil (FA), a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) after focal cerebral ischemia in rats.Methods Totally 48 male Sprague-Dawley (SD) rats were randomly assigned into six groups (n=8 in each group): animals in group ischemia/reperfusion (I/R) only received 120-minute transient middle cerebral artery occlusion (tMCAO); animals in group I/R +FA were administered FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R+FA+GW9662 were administered GW9662 (a PPAR-gamma inhibitor, 1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset and FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R+GW9662 were administered GW9662 (1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R+DMSO were administered 3% DMSO (vehicle of GW9662, 1 ml/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score (NDS) were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) 10 g/L staining.Results NDS was significantly increased in group I/R+FA (12.0(10.0-15.0)), group I/R+FA+GW9662 (10.0 (8.0-12.0)), and in group I/R+FA+DMSO (12.0 (9.0-14.0)) at 72 hours after reperfusion compared with those in group I/R (7.5 (6.0-10.0)). NDS was conspicuously different between group I/R+FA (12.0 (10.0-15.0)) and group I/R+FA+GW9662 (10.0 (8.0-12.0)). MBIVP in group I/R ((45.82 +/- 8.83)%) was significantly greater than that in group I/R+FA ((23.52 +/- 9.90)%), group I/R+FA+GW9662 ((33.17 +/- 7.15)%); MBIVP in group I/R+FA ((23.52 +/- 9.90)%) was significantly smaller than that in group I/R+FA+GW9662 ((33.17 +/- 7.15)%).Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-gamma antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-gamma after focal cerebral ischemia in rats. Chin Med J 2012;125(20):3719-3724