CAJ | 학술논문

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260～310 g,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10 mg/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24 h;S组仅分离血管.再灌注即刻FB组尾静脉注射氟比洛芬酯10 mg/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IM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.
목적 평개불비락분지후처리대대서국조성뇌결혈재관주시신경원조망적영향.방법 건강웅성Wistar대서64지,체중260～310 g,채용수궤수자표법,장기수궤분위4조(n＝16):가수술조(S조)、결혈재관주조(I/R조)、지미구용제조(LM조)화불비락분지10 mg/kg조(FB조).I/R조、LM조화FB조채용개량선전법제비대서국조성뇌결혈재관주손상모형,결혈2h,재관주24 h;S조부분리혈관.재관주즉각FB조미정맥주사불비락분지10 mg/kg,LM조미정맥주사지미구용제1ml/kg,S조화I/R조미정맥주사등용량생리염수.재관주24h시행신경공능결함평분,연후처사대서,취뇌조직,계수결혈측조망신경원,계산신경원조망지수；채용Western blot법검측Bcl-2화Bax단백적표체,계산Bcl-2/Bax비솔.결과 여S조비교,I/R조、LM조화FB조신경공능결함평분화신경원조망지수승고,I/R조화IM조Bcl-2단백표체하조,Bax단백표체상조,Bcl-2/Bax비솔강저(P<0.05)；여I/R조토토비교,LM조각지표차이무통계학의의(P＞0.05),FB조신경공능결함평분화신경원조망지수강저,Bcl-2단백표체상조,Bax단백표체하조,Bcl-2/Bax비솔승고(P<0.05).결론 불비락분지후처리통과조절Bcl-2여Bax적실형,억제신경원조망,감경대서국조성뇌결혈재관주손상.
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-microspheres 1 ml/kg and flurbipofen 10 mg/kg were injected iv at the end of 2 h ischemia in groups LM and FB respectively.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 increased neurologie 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.