塞来昔布对局灶性脑缺血-再灌注大鼠血管内皮生长因子表达的影响  

The effect of celecoxib on the expression of vascular endothelial growth factor in rat ischemia/reperfusion

作　　者：罗传铭[1] 毕桂南[1] 李浩[2] 曹立梅[3] 邱燕东[1] 黎彬如[1] 石胜良[1] 

机构地区：[1]广西医科大学第一附属医院神经内科 [2]桂林医学院附属医院神经内科 [3]上海市第八人民医院神经内科

出　　处：《中国脑血管病杂志》2007年第2期72-75,80,共5页Chinese Journal of Cerebrovascular Diseases

基　　金：广西自然科学基金资助(桂科字0542091)

摘　　要：目的探讨塞来昔布在大鼠局灶性脑缺血-再灌注(I/R)模型中,对血管内皮生长因子(VEGF)表达的影响。方法采用线栓法制作Wistar大鼠大脑中动脉阻塞(MCAO)90min再灌注模型。取192只大鼠分为假手术组12只、等渗盐水组60只、塞来昔布12.5mg/kg和25.0mg/kg治疗组各60只。缺血后30min灌胃,给予各组大鼠等渗盐水或2种剂量的塞来昔布,检测各组大鼠缺血侧额顶部皮质在再灌注6、12、24、48、72h时,前列腺素E2以及VEGF的动态表达。结果①给予塞来昔布12.5mg/kg和25.0mg/kg治疗均能不同程度降低前列腺素E2在缺血侧额顶部皮质中聚集,以24h为显著,前列腺素E2水平分别为(9.8±1.5)和(9.2±0.7)ng/ml,高剂量组表达更为明显(P<0.05)。两组与等渗盐水组的(12.7±1.1)ng/ml比较,差异均有统计学意义(P<0.01)。②2种剂量均能减少脑I/R后12、24、48及72h缺血半暗带VEGF阳性细胞数。脑I/R后脑组织前列腺素E2含量与VEGF表达具有相关性(r=0.768)。结论塞来昔布可能通过抑制环氧化酶2活性,减少前列腺素E2在大脑皮质中聚集,而抑制VEGF的表达。Objective To explore the effect of celecoxib on the expression of vascular endothelium growth factor （VEGF） in a focal cerebral ischemia/reperfusion （I/R） rat model. Methods A model of reperfusion following 1.5 h of middle cerebral artery occlusion （MCAO） in Wistar rats was established with the suture method. A total of 192 rats were divided into sham-operation （n = 12）, isotonic saline solution （n =60）, celecoxib 12. 5 mg/kg （n =60） and celecoxib 25 mg/kg （n =60） groups. Isotonic saline solution or different doses of celecoxib in all groups were administrated intragastrically 30 min after ischemia. The dynamic expressions of prostaglandin E2 and VEGF were detected in the frontal and parietal cortexes on the ischemic sides at 6, 12, 24, 48, and 72 h in all groups. Results Both 12. 5 mg/kg and 25.0 mg/kg celecoxib could reduce the accumulation of prostaglandin E2 to a different extent in the frontal and parietal cortexes on the ischemic sides, especially at 24 h （P 〈0. 01 ）. The levels of prostaglandin E2 were 9. 8 ± 1.5 and 9.2 ±0. 7 ng/ml, respectively, P 〈0. 05. They were more significant in the high-dose group. Both doses of celecoxib could reduce the number＇s of VEGF positive cells in penumba at 12, 24, 48, and 72 h after I/R. There were correlation between prostaglandin E2 content and VEGF expression after I/R （r = 0. 768）. Conclusion Celecoxib may reduce the accumulation of prostaglandin E2 by inhibiting cyclooxygenase-2 activity, and thus inhibiting the expression of VEGF.

关 键 词：环氧化酶2抑制剂 脑缺血 再灌注损伤 血管内皮生长因子类 塞来昔布 

分 类 号：R743.33[医药卫生—神经病学与精神病学]