氟比洛芬酯介导MAPK信号通路保护脑缺血再灌注损伤大鼠血脑屏障功能的机制研究

Mechanism of flurbiprofen axetil on protecting blood-brain barrier function in rats with cerebral ischemia-reperfusion injury by mediating MAPK signaling pathway

目的:探讨氟比洛芬酯介导丝裂原活化蛋白激酶(MAPK)信号通路保护脑缺血再灌注损伤大鼠血脑屏障功能的机制。方法:选取72只健康雄性SD大鼠,随机分为假手术组(Sham组)、脑缺血再灌注损伤组(IR组)和氟比洛芬酯组(F组),每组各24只。建立大鼠脑缺血再灌注经典模型,缺血时间为2 h,再灌注24 h,称湿干重测量脑组织含水量,伊文思蓝(EB)染色法检测大鼠血脑屏障通透性,免疫组化法检测缺血区脑组织的磷酸化p38 MAPK蛋白表达,免疫印迹法检测磷酸化p38 MAPK蛋白相对表达量。结果:F组的脑组织含水量及EB含量高于Sham组,低于IR组(P<0.05);p38 MAPK蛋白阳性表达的等级及相对表达量高于Sham组,低于IR组(P<0.05)。结论:氟比洛芬酯可减轻大鼠脑缺血再灌注损伤,保护血脑屏障功能,机制可能与抑制MAPK信号通路、下调p38 MAPK表达有关。

Objective:To explore the mechanism of flurbiprofen axetil on protecting blood-brain barrier function in rats with cerebral ischemia-reperfusion injury(CIRI)by mediating mitogen-activated protein kinase(MAPK)signaling pathway.Methods:A total of 72 healthy male SD rats were enrolled and randomly divided into sham operation group(Sham group),CIRI group(IR group)and flurbiprofen axetil group(F group),24 cases in each group.The classic model of cerebral ischemia-reperfusion was constructed,the ischemia time was 2 hours.After 24 h of reperfusion,wet/dry weight was weighed to measure the water content of brain tissue.The permeability of blood-brain barrier was detected by Evans blue(EB)staining.The expression of phosphorylated p38 MAPK protein in brain tissue of ischemic area was detected by immunohistochemistry.The relative expression level of phosphorylated p38 MAPK protein was detected by Western blot.Results:The water content and EB content of brain tissue in F group were higher than those in Sham group,which were lower than those in IR group(P<0.05).The positive expression grade and relative expression of p38 MAPK protein in F group were higher than those in Sham group,which were lower than that in IR group(P<0.05).Conclusion:Flurbiprofen axetil can reduce CIRI in rats,and protect blood-brain barrier function.The mechanism may be related to inhibiting MAPK signaling pathway and down-regulating p38 MAPK expression.