Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats

• Published in: Chinese medical journal Vol. 125; no. 20; pp. 3719 - 3724
• Main Authors: Liu, Jun-le, Jin, Jian-Wen, Pei, Shu-Jun, Wang, Chen
• Format: Journal Article
• Language: English
• Published: China Chinese People's Liberation Army General Hospital & Medical School of Chinese People's Liberation Army, Beijing 100853,China 20.10.2012; Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China%Department of Cardiology, Fujian Provincial Unit Hospital, Fujian Health College, Fuzhou, Fujian 350101, China%Chinese People's Liberation Army General Hospital & Medical School of Chinese People's Liberation Army, Beijing 100853,China%Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
• Subjects: Animals; Brain Ischemia - drug therapy; Cyclooxygenase Inhibitors - pharmacology; DMSO; Flurbiprofen - analogs & derivatives; Flurbiprofen - pharmacology; Male; Neuroprotective Agents - pharmacology; PPAR gamma - physiology; Rats; Rats, Sprague-Dawley; 再灌注; 大鼠脑; 局灶性脑缺血; 环氧合酶抑制剂; 神经保护作用; 缺血; 腹腔注射; 过氧化物酶体增殖物激活受体; peroxisome proliferator-activated receptor-γ; neurologic deficit score; flurbiprofen axetil; cerebral ischemia; neuroprotection
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2012.20.022

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-y （PPAR-y） 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-Y 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-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.