氟比洛芬酯后处理对大鼠局灶性脑缺血再灌注时神经元凋亡的影响  

Effects of flurbiprofen postconditioning on neuronal apoptosis induced by focal cerebral ischemia-reperfusion in rats

作　　者：张岫美[2] 陈琳[2] 魏欣冰[2] 于金贵[1] 类维富[1] 

机构地区：[1]山东大学齐鲁医院麻醉科,济南市250012 [2]山东大学医学院药理研究所,济南市250012

出　　处：《中华麻醉学杂志》2011年第8期995-997,共3页Chinese Journal of Anesthesiology

基　　金：山东省自然科学基金（ZR2010HM082）

摘　　要：目的评价氟比洛芬酯后处理对大鼠局灶性脑缺血再灌注时神经元凋亡的影响。方法健康雄性Wistar大鼠64只，体重260～310g，采用随机数字表法，将其随机分为4组（n=16）：假手术组（s组）、缺血再灌注组（I／R组）、脂微球溶剂组（LM组）和氟比洛芬酯10mg／kg组（FB组）。I／R组、LM组和FB组采用改良线栓法制备大鼠局灶性脑缺血再灌注损伤模型，缺血2h，再灌注24h；s组仅分离血管。再灌注即刻FB组尾静脉注射氟比洛芬酯10mg／kg，LM组尾静脉注射脂微球溶剂1ml／kg，s组和I／R组尾静脉注射等容量生理盐水。再灌注24h时行神经功能缺陷评分，然后处死大鼠，取脑组织，计数缺血侧凋亡神经元，计算神经元凋亡指数；采用Western blot法检测Bcl-2和Bax蛋白的表达，计算Bcl-2／Bax比率。结果与s组比较，I／R组、LM组和FB组神经功能缺陷评分和神经元凋亡指数升高，I／R组和LM组Bcl-2蛋白表达下调，Bax蛋白表达上调，Bcl-2／Bax比率降低（P〈0．05）；与I／R组土土比较，LM组各指标差异无统计学意义（P〉0．05），FB组神经功能缺陷评分和神经元凋亡指数降低，Bcl-2蛋白表达上调，Bax蛋白表达下调，Bcl-2／Bax比率升高（P〈0．05）。结论氟比洛芬酯后处理通过调节Bcl-2与Bax的失衡，抑制神经元凋亡，减轻大鼠局灶性脑缺血再灌注损伤。Objective To investigate the effects of flurbiprofen postconditioning on neuronal apoptosis in cerebral cortex induced by focal cerebral ischemia-reperfusion （I/R） in rats. Methods Sixty-four male Wistar rats weighing 260-310 g were randomly divided into 4 groups （n = 16 each） ： group sham operation （group S） ; group I/R; group lipo-microspheres （group LM） and group flurbiprofen （group FB）. Focal cerebral I/R was induced by occluding left middle cerebral artery for 2 h followed by 24 h reperfusion in groups I/R, LM and FB. Lipo-micro- spheres 1 ml/kg and flurbipofen 10 mg/kg were injected iv at the end of 2 h ischemia in groups LM and FB respec- tively. The neurologic deficit was assessed and scored （0 = normal, 4 = unconscious） at 24 h of reperfusion. The animals were then sacrificed and their brains were removed for detection of neuronal apoptosis （ by TUNEL） and the expression of Bcl-2 and Bax protein （by Western blot） in cerebral cortex. Results Cerebral I/R significantly in- creased neurologic deficit scores and neuronal apoptosis index as compared with group S. Bcl-2 protein expression was significantly down-regulated and Bax protein expression up-regulated and Bcl-2/Bax ratio decreased in group I/R compared with group S. Flurbiprofen postconditioning significantly attenuated I/R-induced increase in neurologic dificit scores, and neuronal apoptosis index and decrease in Bcl-2/Bax ratio in group FB compared with group I/R. Conclusion Flurbiprofen postconditioning can attenuate focal cerebral I/R injury by correcting the imbalance between Bcl-2 and Bax expression and inhibiting neuronal apoptosis in cerebral cortex.

关 键 词：氟比洛芬 再灌注损伤 脑 细胞凋亡 神经元 

分 类 号：R965.3[医药卫生—药理学]