己美舒利对大鼠脑损伤后脑水肿及髓过氧化物酶、金属蛋白酶-2的影响

目的阐明环氧化酶-2（cox-2）抑制剂尼美舒利对大鼠创伤性脑损伤的影响与机制。方法健康雄性SD大鼠40只,随机分为4组：对照组、尼美舒利组【6mg／（kg·d）1、创伤组、创伤＋尼美舒利组f6mg／（kg·d）1。利用300g,／m的自由落体重力打击装置创建SD大鼠创伤性脑损伤模型,创伤后24h进行神经功能评分,随后处死动物并断头取脑组织。脑水肿及血脑屏障通透性分别以干湿重称重法及伊文思蓝染色测定,测量脑组织中髓过氧化物酶（MPO）及金属蛋白酶-2（MMP-2）的含量以及病理组织形态学观察。结果创伤组脑组织含水量及EB含量比对照组明显增加（P〈0．05）,创伤＋尼美舒利组脑组织含水量及EB含量比创伤组明显减少（P〈0．01）。创伤＋尼美舒利组脑组织MMP-2、MPO表达比创伤组减少,MPO蛋白表达与MMP-2蛋白表达呈正相关。结论在创伤性脑损伤大鼠模型中,尼美舒利通过保持血脑屏障完整性,抑制MPO、MMP-2的过度表达（可能通过其抗炎能力）而发挥其神经保护作用。

Effect of nimesulide against traumatic brain injury-induced brain edema, myelopreoxidase and metalloproteinase-2 changes in rats

Objective To clarify the effects and mechanisms of COX-2 inhibitor-nimesuhde on rats with traumaUc brain injury-induced. Methods Forty male Sprague-Dawley rats were divided into four groups, which were control group, nimesulide group [6 mg/（kg＇d）], trauma group and trauma ＋ nimesu]ide group [6 mg/（kg＇d）]. Sprague-Dawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g/m weight-height impact. Twenty- four hours after the injury, neurological examination scores were measured, the animals were decapitated and brain tissues were taken. Brain edema and blood-brain barrier （BBB） permeability were evaluated by wet-dry weight method and Evans blue （EB） extravasation respectively. In brain tissue, myelopreoxidase and metalloproteinase-2 were mea- sured and histopathological was observed. Results In trauma group, water contents and EB contents were significantly higher than that of control group （P 〈 0.05）. In trauma＋nimesulide group, water contents and EB contents were signifi- cantly lower than that of trauma group （P 〈 0.01）. In trauma＋nimesulide group, the content of MPO protein and MMP-2 protein were significantly lower than that of trauma group, the change of MPO protein were positively correlated with the change of the MMP-2 protein. Conclusion Nimesulide exerts neuroprotective effect by preserving BBB permeabil- ity and by inhibiting the overexpression of myclopreoxidase and metalloproteinase-2 （probably by its anti-inflammatory properties） in the diffuse brain injury model.