摘要
目的探讨马来酸罗格列酮对脑缺血后炎症反应影响,以评价马来酸罗格列酮对脑缺血损伤的保护作用。方法大鼠大脑中动脉线栓法建立局灶性脑缺血模型,缺血即刻及缺血2h后经插入胃管分别灌入马来酸罗格列酮0.5,2,4mg·kg-1,测定缺血24h后,大鼠脑肿胀情况,脑组织髓过氧化物酶(MPO)活性,以及缺血2h并再灌注22h后脑组织髓过氧化物酶(MPO)活性和IL-6mRNA表达的影响。结果马来酸罗格列酮0.5mg·kg-1对脑肿胀改变无明显影响(P>0.05),2,4mg·kg-1实验组脑肿胀可见明显减轻(P<0.05),但二者之间无显著差异;各种不同剂量的马来酸罗格列酮可明显抑制缺血及再灌注大鼠的MPO水平(P<0.05,P<0.01),且抑制程度呈剂量相关;马来酸罗格列酮0.5,2mg·kg-1可一定程度降低缺血再灌注脑组织IL-6 mRNA表达的水平(P<0.05),两剂量组之间有显著差异。结论马来酸罗格列酮可有效抑制脑缺血和再灌注后脑损伤。
Abstract
OBJECTIVE To evaluate the neuroprotective effect of rosiglitazone maleate against brain ischemic injury by investigating the effects of rosiglitazone maleate on the inflammation following cerebral ischemia/reperfusion.METHODS Focal cerebral ischemia was induced by the intraluminal suture for middle cerebral artery occlusion.Rosiglitazone maleate 0.5,2 and 4 mg·kg-1 were taken orally immediately or 2 h after MCA occlusion, respectively.And the effects of rosiglitazone maleate on brain swell,myeloperoxidase and interleukin-6 mRNA level in brain tissue were evaluated after MCA occlusion and reperfusion.RESULTS No effect was found on brain swell in the group treated with RSG 0.5 mg·kg-1. The significant reduction of brain swell was observed in group treated with 2 and 4 mg·kg-1 RSG.All different doses of RSG reduced MPO activity in brain tissue with a dose-dependent manner after MCA occlusion and reperfusion. The reduction of IL-6 mRNA was found in 2 rosiglitazone maleate treatment groups(P<0.05),and there was significant difference between 2 groups. CONCLUSION Rosiglitazone maleate ameliorated brain ischemic injury after an 24 h MCA occlusion and inhibited the inflammatory response after an ischemia-reperfusion in this study.
关键词
马来酸罗格列酮 /
大鼠 /
脑缺血 /
髓过氧化物酶 /
白细胞介素-6
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Key words
rosiglitazone maleate /
rat /
brain ischemia /
reperfusion /
myeloperoxidase
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熊南翔;孙帆;赵洪洋;向继洲.
马来酸罗格列酮对大鼠脑缺血及再灌注后炎症的影响[J]. 中国药学杂志, 2006, 41(17): 1301-1304
XIONG Nn-xing;SUN Fn;ZHO Hong-yng;XING Ji-zhou.
Effect of Rosiglitazone Maleate on Inflammation Following Cerebral Ischemia/Reperfusion in Rats [J]. Chinese Pharmaceutical Journal, 2006, 41(17): 1301-1304
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参考文献
[1] CAMPBELL I W. The clinical significance of PPAR gamma agonism[J] .Curr Mol Med，2005，5(3)：349-363.
[2] ITO K，SHIMADA J，KATO D，et al. Protective effects of preischemic treatment with pioglitazone，a peroxisome proliferator-activated receptor-gamma ligand，on lung ischemia-reperfusion injury in rats[J] . Eur J Cardiothorac Surg，2004，25(4)：530-536.
[3] ITO H，NAKANO A，KINOSHITA M，et al. Pioglitazone，a peroxisome proliferator-activated receptor-gamma agonist，attenuates myocardial ischemia/reperfusion injury in a rat model[J] .Lab Invest，2003，83(12)：1715-1721.
[4] ABDELRAHMAN M，SIVARAJAH A，THIEMERMANN C. Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury，inflammation and shock[J] .Cardiovasc Res，2005，65(4)：772-781.
[5] BECKER K J．Inflammation and acute stroke[J] ．Curr Opin Neurol，1998，11(1)：45-49．
[6] RITRER L，COULL B，DAVISGOMAN G，et al. Leukocytes accumulate in the cerebral microcrculation during the first hour of reperfusion fo1lowing stroke[J] .FASEB J，1998，12：180-188．
[7] IALENTI A，GRASSIA G，DI MEGLIO P，et al. Mechanism of the anti-inflammatory effect of thiazolidinediones： relationship with the glucocorticoid pathway[J] .Mol Pharmacol，2005，67(5)：1620-1628.
[8] ARTWOHL M，HOLZENBEIN T，FURNSINN C，et al. Thiazolidinediones inhibit apoptosis and heat shock protein 60 expression in human vascular endothelial cells[J] .Thromb Haemost，2005，93(5)：810-815.
[9] PISTROSCH F，HERBRIG K，OELSCHLAEGEL U，et al. PPARgamma-agonist rosiglitazone increases number and migratory activity of cultured endothelial progenitor cells[J] .Atherosclerosis，2005，183(1)：163-167.
[10] GAME B A，MALDONADO A，HE L，et al. Pioglitazone inhibits MMP-1 expression in vascular smooth muscle cells through a mitogen-activated protein kinase-independent mechanism[J] .Atherosclerosis，2005，178(2)：249-256.
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脚注
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