帕瑞昔布对大鼠局灶脑缺血-再灌注脑组织GFAP及IL-1β、TNF-α的影响  

Effect of parecoxib pretreatment on the expression of GFAP,IL-1β and TNF-α in rat brain against focal cerebral ischemia-reperfusion injury in rats

作　　者：刘少星[1] 刘丹彦[2] 代月娥[3] 刘文良[2] 

机构地区：[1]四川省成都市第二人民医院麻醉科,610017 [2]重庆医科大学第一附属医院麻醉科 [3]四川省医学科学院四川省人民医院麻醉科

出　　处：《临床麻醉学杂志》2012年第2期171-174,共4页Journal of Clinical Anesthesiology

基　　金：重庆市卫生局课题面上项目(编号:20102003)

摘　　要：目的探讨帕瑞昔布术前给药对大鼠局灶性脑缺血-再灌注损伤的影响及其机制。方法雄性SD大鼠64只,体重250～300g,随机均分为四组:假手术组(S组),单纯缺血-再灌注组(IR组),缺血-再灌注+帕瑞昔布5mg/kg术前给药组(P5组),缺血-再灌注+帕瑞昔布10mg/kg术前给药组(P10组)。采用线栓法制作大鼠大脑中动缺血2h再灌注24h模型,在缺血2h及再灌注24h时行神经功能缺损评分;TTC染色观察脑梗死体积及体积百分比;HE染色观察海马CA1区神经元病理改变;放射免疫法检测缺血侧额区皮质中前列腺素E2(PGE2)、白细胞介素1β(IL-1β)及肿瘤坏死因子α(TNF-α)含量;免疫组化法检测缺血侧星形胶质细胞(AS)中胶质纤维酸蛋白(GFAP)的表达。结果缺血2h、再灌注24h时IR、P5、P10组神经功能缺损评分均高于S组(P<0.01);再灌注24h时P10组神经功能缺损评分显著低于IR组(P<0.05)。P5、P10组脑梗体积及体积百分比均低于IR组(P<0.01)。P5、P10组PGE2、IL-1β、TNF-α含量低于IR组,且P10组显著低于P5组(P<0.05或P<0.01)。IR组海马区GFAP阳性细胞数显著多于S组;P5、P10组GFAP阳性细胞数显著少于IR组,且P10组明显低于P5组(P<0.05或P<0.01)。结论帕瑞昔布术前给药对大鼠局灶性脑缺血-再灌注损伤具有保护作用,其机制可能与减少脑组织中PGE2含量、抑制AS过度激活、减少IL-1β、TNF-α释放有关。Objective To investigate the effect and the mechanism of parecoxib pretreatment on brain against focal cerebral ischemia-reperfusion（IR） injury in rats. Methods Sixty-four male SD rats weighing 250-300 g were randomly divided into four groups （n= 16 each） .. shame operation （group S） ; focal cerebral IR（group IR）; parecoxib 5/10 mg/kg（30 minutes before ischemia）＋focal cerebral IR（group Ps, P10 ）. Middle cerebral artery occlusion （MCAO）models were made by reforming Longa suture method in SD rats. The infarct volume and the infarct volume fraction were detected by TIC staining, the neurologic deficit scores（NDS） in each group was recorded at 2 h of occlusion and 24 h of repeffusion, the pathological changes in CA1 region of hippocampus were detected by HE staining, radioimmunoassay technique was used to determine the content of PGE2, IL-1β, TNF-a in rat brain, the levels of protein GFAP in AS were detected by immunohistochemistry. Results The NDS were higher in group IR,P5 ,P10 than in group S at 2 h of ischemic and 24 h of repeHusion（P〈0. 05 or P〈0. 01）. The NDS were lower in group Pl0 than that in group IR at 24 h of reperfusion（P〈0. 05）. The infarct volume was significantly smaller in group P5, P10 than in group IR（P〈0. 01）. The content of PGE2 ,IL-1β,TNF-a in brain in group P5 ,Pl0 were significantly lower than in group IR,and the group Pl0 was significantly lower than the group P5. The number of GFAP positive cells in CA1 region of hipocampus in group IR is more than group S, Ps ,P10 were significantly less than in group IR and group P10 significantly less than in group P5 （P〈0. 05 or P 〈0. 01 ）. Conclusion Pretreatment with parecoxib can protect the brain from focal cerebral IR injury by reduced the content of PGE2, inhibit the overactivation of AS, reduce IL-1β,TNF-a release in rat brain.

关 键 词：帕瑞昔布 脑缺血-再灌注 前列腺素E2 细胞因子 胶质纤维酸蛋白 

分 类 号：R965[医药卫生—药理学]