冰片增强依达拉奉对脑缺血再灌注损伤大鼠抗氧化作用研究

Study on borneol enhancing the antioxidant eff ect of edaravone in rats with the cerebral ischemia-reperfusion

目的探究冰片协同依达拉奉对脑缺血再灌注损伤大鼠的抗氧化作用的影响。方法60只SD大鼠随机分为假手术组,脑缺血再灌注组,脑缺血再灌注加依达拉奉组,脑缺血再灌注加冰片组,脑缺血再灌注加依达拉奉加冰片组。I/R模型构建后观察神经功能缺损症状,检测脑组织水肿程度和脑梗死面积,氧化因子(MDA,SOD,GSH)水平,炎性细胞因子(IL-6,TNF-α,IL-1β)水平,血脑屏障紧密连接蛋白(ZO-1,Occludin,Claudin-5)表达。结果I/R组大鼠出现神经功能评分增加,脑水肿程度和脑梗死面积增加。依达拉奉与冰片不同程度减轻以上病理改变,但仅有依达拉奉与冰片联合使用表现改善明显。I/R组大鼠氧化因子水平增加,抗氧化因子水平降低,且炎性细胞因子水平增加,依达拉奉与冰片联合使用抗氧化与抗炎效应最强,优于药物单用。I/R降低了大鼠脑组织中血脑屏障紧密连接蛋白表达,依达拉奉与冰片能够不同程度的增加ZO-1,Occludin,Claudin-5表达,依达拉奉与冰片联合使用能够恢复这些蛋白表达水平至基线。结论依达拉奉与冰片能不同程度改善脑缺血再灌注后病理症状。冰片能够增强依达拉奉抗氧化、抗炎作用,机制可能与协同抑制缺血后ZO-1,Occludin,Claudin-5表达下调,保护血脑屏障有关。

Objective To explore the effect of borneol combined with edaravone on the cerebral ischemia-reperfusion in rats.Methods A total of 60 SD rats were randomly divided into sham operation group(Sham),cerebral ischemia-reperfusion group(I/R),cerebral ischemia-reperfusion plus edaravone group(Edaravone),cerebral ischemiareperfusion plus borneol group(Borneol),cerebral ischemia-reperfusion plus edaravone plus borneol group(Edaravone+Bor).After the I/R model was established,the symptoms of the neurological defi cit were observed,the degree of the brain tissue edema and cerebral infarction area,the levels of the oxidation factors(MDA,SOD,GSH)and the infl ammatory cytokines(IL-6,TNF-α,IL-1β),and the expression of the blood-brain barrier tight junction protein(ZO-1,Occludin,Claudin-5)were detected.Results The neurological function score,cerebral edema degree and cerebral infarction area were increased in the I/R group.Edaravone and borneol reduced these pathological changes to varying degrees,but only the combined use of edaravone and borneol showed signifi cant improvement.In the I/R group,the levels of the oxidative factors were increased,the levels of the antioxidant factors were decreased,and the levels of the infl ammatory cytokines were increased.The combination of edaravone and borneol had the strongest antioxidant and anti-infl ammatory eff ects,which was better than the single use of either drug.I/R decreased the expression of the blood-brain barrier tight junction protein in the brain tissue of rats.Edaravone and borneol increased the expression of ZO-1,Occludin and Claudin-5 to varying degrees.The combined use of edaravone and borneol restored the expression levels of these proteins to baseline.Conclusion Edaravone and borneol can improve the pathological symptoms after the cerebral ischemia-reperfusion to varying degrees.Borneol can enhance the antioxidant and anti-inflammatory eff ects of edaravone.The mechanism may be related to the cooperative inhibition of the down-regulation of the ZO-1,Occludin and Claudin-5 expression after ischemia,and the protection of the blood-brain barrier.