丁苯酞对脑缺血再灌注损伤大鼠MMP-9活性和血脑屏障通透性的影响

Effect of dl-3n-butylphtalid on the the activity of MMP-9 and the permeability of the blood-brain barrier on rats with focal cerebral ischemia/reperfusion injury

目的探讨丁苯酞对脑缺血再灌注损伤大鼠的保护作用。方法通过线栓法制备大鼠局灶性脑缺血再灌注损伤模型,腹腔注射丁苯酞,于脑缺血再灌注后6h、12h、24h后用免疫组织化学的方法观察损伤侧脑组织MMP-9活性及基底膜成分Ⅳ型(collagenⅣ)胶原表达的变化。同时测定伊文思兰的含量观察损伤侧脑组织血脑屏障通透性。结果随缺血再灌注时间延长,MMP-9活性、EB含量逐渐增加,24h达峰,Ⅳ型胶原的表达逐渐减少,各组之间表达均具有统计学意义(P<0.05);丁苯酞处理组MMP-9活性、EB含量各个时间点明显低于缺血再灌注组,相同时间点Ⅳ型胶原的表达增加(P<0.05)。结论丁苯酞可抑制脑缺血再灌注损伤大鼠MMP-9的表达,增加基底膜Ⅳ型胶原的表达,降低血脑屏障通透性,从而发挥脑保护作用。

Objective To explor the protective effect of dl-3n-butylphtalide on ischemia-reperfusion injury in rat brain.Methods With a model of reversible middle cerebral artery occlusion(MCAO) in rats,dl-3n-butylphtalide was injected intraperitoneally.The MMP-9 activity was measured,the express of the collagen Ⅳ was detected by immunohistochemistry,and blood brain barrier(BBB) permeability was evaluated by detection of extravasated Evans blue(EB) separately investigated over a time course ranging from 6h to 24h(n=5) of reperfusion following two hours of cerebral ischemia.Results The activity of MMP-9 significantly elevated at 24h(P<0.05) and reached the peak after 24h following I/R.The contents of EB increased progressively over time after I/R,and reached maximum levels at 24h(P<0.05).The contents of collagen Ⅳ reduce progressively(P<0.05).The contents of EB and the activity of MMP-9 in the dl-3n-butylphtalide group were reduced significantly in comparison with the ischemia/reperfusion(I/R) group,and the express of the collagen Ⅳ increased at the same time point(P<0.05).Conclusion Dl-3n-butylphtalide may suppress the activity of MMP-9,increase the express of the collagen Ⅳand mitigate the permeability of the blood-brain barrier on rats with focal cerebral ischemia/reperfusion injury.