中文摘要：

目的 观察过氧化物酶体增殖物激活受体γ（PPARγ）在脑缺血再灌注损伤中核移位的改变,并初步探讨该改变在脑缺血损伤中的意义.方法 健康雄性SD大鼠制作大脑中动脉阻塞再灌注模型,缺血60 min,再灌注4、8、24 h.采用Western blot法、免疫组织化学和免疫荧光染色法观察PPARγ核移位的改变以及PPARγ激动剂和拮抗剂对PPARγ核移位的影响;同时,2,3,5-氯化三苯四唑（TTC）染色法观察脑梗死体积的改变.结果 （1）Western blot检测显示,脑缺血再灌注4 h即引起PPARγ核蛋白增加,同时胞质蛋白减少,差异具有统计学意义.随再灌注时间的增加,PPARγ核移位呈时间依赖性增强.免疫组织化学和免疫荧光染色均显示,与假手术组48.3%相比,缺血再灌注24 h胞核PPARγ阳性增加到80.3%,差异具有统计学意义（t=8.63,P=0.00）.（2）与单纯缺血再灌注组相比,PPARγ激动剂进一步增加PPARγ核蛋白表达,同时减少胞质蛋白表达,差异均具有统计学意义;相反,PPARγ抑制剂GW9662则降低核蛋白水平而增加胞质表达,差异均具有统计学意义.（3）经TTC染色显示,与单纯缺血再灌注组相比,PPARγ激动剂使脑梗死体积减少了48.40%（15.46±4.94与29.96 ±3.39,t=5.93,P=0.00）;而PPARγ抑制剂则使脑梗死体积增加了58.95%（47.62±4.93与29.96±3.39,t=7.23,P=0.00）.结论 脑缺血再灌注损伤使大鼠PPARγ核移位增加,该改变可能是脑组织的一种自我保护性反应.

英文摘要：

objective To examine nuclear transIocation of peroxisome proliferator-activated receptor γ（PPARγ）in rats following focal cerebral ischemia/reperfusion（I/R）,and to explore the significance of altered PPARγ,nuclear translocation in ischemic brain injury.Methods Healthy adult male SD rats underwent 60-min cerebral artery occlusion followed by reperfusion of 4,8,or 24 h,respectively.The cytoplasmic-to-nuclear shuttling of PPARγ was characterized by Western blot,immunohistochemical and immunofluoreseence staining.The effects of PPARγ agonist rosiglitazone （Ros） and antagonist GW9662 on I/R-induced PPARγ nuclear translocation were also examined in the present study. Furthermore,TTC staining war adopted to determine the change in cerebral infarction volume. Results （1）Western blot analysis revealed an increase of PPARγ in the nucleus and a simultaneous reduction in the cytosol following ischemia and reperfusion for 4 h（tcytosol=9.03,tmuclear=27.19,P=0.00）.Prolonged the reperfusion further enhanced this I/R induced PPARγ translocation in a time-dependent manner.Using immunohistochemistry and immunofluorescence,nuclear PPAR γ positive staining increased from 48.3%in the sham control to 80.3% following ischemia and reperfusion for 24 h.（2）Western blot analysis revealed that PPARγ agonist Ros further increased I/R-induced nuclear enrichment of PPARγ,whereas PPARγ antagonist GW9662inhibited I/R-stimulated change in PPARγ.（3）When compared to the L/R group using TTC staining,Ros treatment significantly decreased the infarction volume by 48.40%（15.46±4.94 versus 29.96±3.39,t=5.93.P=0.00）,whereas GW9662 increased by 58.95%（47.62±4.93 versus 29.96±3.39,t=7.23,P=0.00）.Conclusions Cerebral I/R injury induces PPARγ translocation from the cytosol to the nucleus.This change may represent an intrinsic neuroprotective response against brain I/R injury.