摘要
目的 探讨氟比洛芬酯预先给药对大鼠全脑缺血再灌注损伤的影响。方法健康雄性SD大鼠84只，体重200～350g，随机分为4组（n=21）：假手术组（S组）、缺血再灌注组（IR组）、氟比洛芬酯5mg／kg组（F1组）和氟比洛芬酯10mg／kg组（F2组）。采用夹闭双侧颈总动脉联合低血压法建立全脑缺血再灌注模型。F1，2组分别于缺血前15min静脉注射氟比洛芬酯5、10mg／kg。于再灌注6h（T1）、24h（T1）、72h（L）时随机取7只大鼠行神经功能缺陷评分（NDS），采用放射免疫法测定血清肿瘤坏死因子α（TNFα）、白细胞介素1β（IL-1β）的浓度，RT-PCR法测定海马组织核因子-kB（NF-kB）mRNA及细胞间粘附分子-1（1CAM—1）mRNA的表达水平，并观察海马CA1区病理学结果。结果与S组比较，其余3组T1-3时NDS升高，海马组织ICAM—1 mRNA、NF-kB mRNA表达上调，T1,2时血清TNF—α浓度升高，T1-3时血清IL-1β浓度升高（P〈0．05或0．01）；与IR组比较，F1,2组T1,3时NDS降低，海马ICAM-1mRNA、NF-kBmRNA表达下调，T1,2时血清TNF-α浓度降低T1-3时血清IL-1β浓度降低（P〈0．05或0．01）；与F1组比较，F2组t2,3时海马ICAM-1mRNA表达下调，己时血清IL-1β浓度降低（P〈005或0．01）。IR组、F1组及F2组海马组织病理学损伤程度依次减轻。结论氟比洛芬酯预先给药可减轻大鼠全脑缺血再灌注损伤，且呈剂量依赖性，其机制可能与抑制海马组织炎性反应有关。
Objective To investigate the effects of pretreatment with flurbiprofcn on global cerebral ischemia-reperfusion （IR） injury in rats and the mechanism involved. Methods Eighty-four male SD rats weighing 200-350 g were randomly divided into 4 groups （ n = 2t each） ： group Ⅰ sham operation （group S） ; group Ⅱ global cerebral IR （group IR）; group Ⅲ flurbiprofen 5 mg/kg ＋ global cerebral IR （group F1 ） and group Ⅳ flurbiprofen 10 mg/kg ＋ global cerebral IR （group F2）. Global cerebral ischemia was induced by 20 min occlusion of bilateral common carotid arteries combined with hypotension （ MAP maintained at 35-45 mmHg）. In group F1 anti F2 flnrbiprofen 5 and 10 mg/kg was injected iv at 15 inin before ischemia respectively. The neurological deficit score （NDS） was assessed （0 = normal, 100 = brain death） at 6 h （T1）, 24 h （T2） and 72 h （T3） of reperfnsion by the same observer. Blood samples were taken from left internal jugular vein. And then the animals were killed and brains removed tbr delennination of serum concentrations of TNF-α and IL-1β （using radioimmunoassay）, expression of nuclear factor-kappa B （NF-kB） mRNA and intercellular adhesion molecule-1 （ICAM-1） mRNA in hippocampus （by RT-PCR）, and microscopic examination. Results Compared with group S, NDS at T1- 3 was significantly increased, expression of NF-kB mRNA and ICAM-I mRNA at T1-3 was upregulated and serum concentrations of TNF-α at T1,2 and IL-1β at T1,3 were significantly increased in the other three groups （ P 〈 0.05 or 0.01 ）. Compared with group 1R, NDS at T1.3 was significantly decreased, expression of NF-kB mRNA and ICAM-1 mRNA at T1.3 was down-regulated and serum concentrations of TNF-α at T1.2 and IL-1β at T1,3 were significantly decreased in group F1.2 （ P 〈 0.05 or 0.01 ）. The expression of ICAM-i mRNA at T1.3 was down-regulated and serum concentrations of IL-1β at T2 significantly decreased in group F2 compared with group F, （P 〈 0.05 or 0.01）
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2009年第10期945-949,共5页
Chinese Journal of Anesthesiology
关键词
氟比洛芬
脑
再灌注损伤
海马
Flurbiprofen
Brain
Reperfusion injury
Hippocampus
