氧化苦参碱对脑梗死后血-脑脊液屏障保护作用的研究

The protevtive effects of oxymatrine on the blood-cerebrospinal fluid barrier after cerebral infarction

目的 探讨缺血性脑卒中(CI)损伤后RAGE/NF-κB通路的动态变化及氧化苦参碱保护CI后血-脑脊液屏障(BCFB)通透性增加的具体机制。方法 应用线栓法制备大脑中动脉闭塞模型,并将大鼠随机分为4组:假手术组、缺血组和干预组分别为氧化苦参碱(OMT) 60 mg·kg^(-1),OMT120mg·kg^(-1)。在脑缺血24 h时应用干湿重法测定脑水肿、伊文思蓝渗出评估BCFB的完整性,并从组织学、蛋白和mRNA水平检测IS脑组织中晚期糖基化终末产物受体(RAGE)、核因子-κB (NF-κB)、肿瘤坏死因子α (TNF-α)及基质金属蛋白酶-9 (MMP-9)的变化;以及OMT干预对其表达的影响。结果 OMT 120mg·kg-1组可明显降低脑含水量,减少伊文思蓝的渗出;高剂量OMT可降低RAGE、TNF-α、MMP-9的表达,并抑制NF-κB核转位。结论 OMT能够抑制IS后炎症反应,保护BCFB完整性,其作用可能通过RAGE/NF-κB信号通路介导。

Objective To explore the changes of RAGE/NF-κB signaling pathway after ischemic infarction(CI)injury and the specific mechanism of oxymatrine(OMT)in protecting the increase of blood-cerebrospinal fluid barrier(BCFB)permeability after IS.Methods The middle cerebral artery occlusion model of rats was established by thread embolism method,and the rats were randomly divided into four groups:sham operation group,ischemia group and intervention group(oxymatrine 60 mg·kg-1 and oxymatrine 120 mg·kg 1,respectively).After 24 hours of cerebral ischemia,brain edema and Evans blue exudation were measured by dry-wet gravimetric method to evaluate the integrity of BCFB,and the changes of RAGE,NF-κB,TNF-αand MMP-9 in ischemic brain tissue were detected from histological,protein and mRNA levels.The effect of OMT was also measured on its expression.Results OMT could significantly reduce brain water content and Evans blue exudation.High dose OMT could decrease the expression of RAGE,TNF-αand MMP-9,and inhibit the nuclear translocation of NF-κB.Conclusion OMT can inhibit the inflammatory reaction after cerebral ischemia and protect the integrity of BCFB,which may be mediated by RAGE/NF-κB signaling pathway.