帕瑞昔布钠对大鼠局灶脑缺血再灌注损伤的影响

摘要

Objective To investigate the effect and the mechanism of parecoxib pretreatment on focal cerebral ischemia-reperfusion injury in rats by measuring the content of TXA2,PGI2,IL-1 β,TNF-α,PGE2 and TXA2/PGI2 in plasma.Methods Fourty-eight male SD rats were randomly divided into 4 groups (n =12):sham operation group (S) ; model group (I/R) ; parecoxib 5/10 mg/kg group (L,H).Middle cerebral artery occlusion models were made by reforming Longa suture method in SD rats.Rats in L and H group were injected 5 mg/kg and 10 mg/kg parecoxib,respectively,through internal jugular vein 30 minutes before ischemia.Rats in S group and I/R group were given equal volume of normal saline.After ischemia for 90 mins and reperfusion for 24 hours,respectively,the neurologic deficit scores were measured,the pathological changes in CA1 region of hippocampus were detected by HE staining,radioimmunoassay technique was used to determine the content of TXA2,PGE2,TNF-α,IL-1 β and TXA2/PGI2 in plasma.Results Pretreatment with parecoxib significantly decreased the content of TXA2,PGE2,TNF-α,IL-1 β and TXA2/PGI2 in plasma,mitigated the injury in CA1 region of hippocampus and improved the nerve function of rats with focal cerebral ischemia-reperfusion injury.Conclusion Parecoxib can protect the brain from focal cerebral I/R injury by reducing the content of TXA2,PGE2,TNF-α,IL-1 β and the ratio of TXA2/PGI2 in plasma of rats.%目的 探讨帕瑞昔布钠对大鼠局灶性脑缺血再灌注损伤的影响并通过检测血浆中TXA2、PGI2、PGE2、TNF-d、IL-1β含量来探讨其可能机制.方法 雄性SD大鼠48只,随机分为4组(n=12):假手术组(S组),模型组(I/R组),帕瑞昔布钠5 mg/kg处理组(L组),帕瑞昔布钠10mg/kg处理组(H组).线栓法制作大鼠大脑中动脉缺血90 min再灌注24 h模型,L组、H组在缺血30 min前经颈内静脉分别注入经生理盐水等容积稀释的5 mg/kg和10 mg/kg帕瑞昔布钠注射液,S组及I/R组给予等容积生理盐水.在缺血90 min及再灌注24 h行神经功能缺失评分,HE染色观察海马CA1区神经元病理改变,放射免疫法检测血浆中TXA2、PGI2、PGE2、TNF-α、IL-1 β含量并计算TXA2/PGI2比值.结果 帕瑞昔布钠能显著降低血浆中TXA2、PGE2、TNF-α、IL-1 β含量及减小TXA2/PGI2比值,减轻缺血侧海马CA1区损伤,改善大鼠局灶性脑缺血再灌注后神经功能.结论 帕瑞昔布钠对局灶性脑缺血再灌注损伤具有较好的抗炎保护作用,其机制可能与通过降低血浆TXA2、PGE2、TNF-α、IL-1 β含量及减小TXA2/PGI2比值有关.