帕瑞昔布钠预先给药对大鼠局灶脑缺血再灌注血脑屏障通透性的影响

Effect of Parecoxib Sodium Pretreatment on Permeability of Blood-Brain Barrier in a Rat Model of Focal Cerebral Ischemia-reperfusion Injury

目的探讨帕瑞昔布钠预先给药对大鼠局灶性脑缺血再灌注血脑屏障通透性的影响及机制.方法60只雄性SD大鼠,体重300 g左右,随机分为5组,每组12只:假手术组(S组)、缺血再灌注组(I/R组)、帕瑞昔布钠5 mg/kg组(L组)、帕瑞昔布钠7.5 mg/kg组(M组)、帕瑞昔布钠10 mg/kg组(H组).线栓法制作大鼠大脑中动缺血90 min再灌注24 h模型,缺血30 min前L、M、H组分别在经右侧颈内静脉注入等容积的5mg/kg、7.5 mg/kg、10 mg/kg帕瑞昔布钠注射液,S、I/R组给予等容积生理盐水;各组大鼠在缺血90 min及再灌注24 h时行神经功能缺损评分,酶联免疫吸附实验(ELISA)法测定血浆中S100β、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)含量,测量脑组织干湿重比(W/D)及脑组织伊文思蓝(EB)含量.结果大鼠局灶性脑缺血90 min再灌注24 h帕瑞昔布钠预先给药(5 mg/kg、7.5 mg/kg、10 mg/kg)能显著降低血浆中S100β、TNF-α、IL-1β含量,降低脑组织W/D及脑组织EB含量,10 mg/kg帕瑞昔布钠预先给药可改善大鼠局灶性脑缺血再灌注后神经功能.结论帕瑞昔布钠预先给药可改善大鼠局灶性脑缺血再灌注血脑屏障通透性,减轻脑损伤,其机制可能与抑制炎性反应有关.

Objective To investigate the effect and the mechanism of parecoxib sodium pretreatment on permeability of blood-brain barrier in a rat model of focal cerebral ischemia-reperfusion injury.Methods Sixty male SD rats weighing 300 g were randomly divided into 5 groups（n=12 each） ： sham operation group（group S）; focal cerebral I/R group（group I/R）; parecoxib sodium 5 mg/kg pretreatment group（group L）;parecoxib sodium7.5mg/kg pretreatment group（group M）; parecoxib sodium 10 mg/kg pretreatment group（group H）. Middle cerebral artery occlusion models were made by reforming Longa suture method in SD rats.Thirty minutes before ischemia, rats in group L, M and H were injected with 5 mg/kg、 7.5 mg/kg and 10mg/kg parecoxib sodium through the internal jugular vein. Group S and group I/R received equal volume of normal saline. ELISA technique was used to determine the content of S100β, TNF-α, IL-1β in Plasma. The changes of cerebral water content and the Evans Blue exudation from brain capillaries were observed. Results Pretreated with parecoxib sodium（5 mg/kg、 7.5 mg/kg and 10 mg/kg）, the content of S100β, TNF-α, IL-1β in plasma were reduced. The cerebral water content and the EB in brain were reduced. Pretreated with parecoxib sodium 10 mg/kg,Longa scores were reduced. Conclusion Pretreatment with Parecoxib can protect blood-brain barrier against focal cerebral I/R injury by inhibition of the inflammatory reaction.