蛛网膜下腔出血后早期海马ADAMTS-1的表达与血脑屏障通透性的相关性研究

目的研究大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中ADAMTS-l(a disintegrin-like and metalloproteinase with thrombospondin type l motifs)表达情况及其与血脑屏障通透性的关系,初步探讨ADAMTS-l在实验性大鼠SAH后早期脑损伤(early brain injury,EBI)中的作用。方法成年雄性SD大鼠108只,分假手术组和SAH组。采用大鼠视交叉前池注血模型,于SAH后6、12、24、48、72 h时间点,应用Western-Blotting和RT-PCR法检测大鼠海马ADAMTS-1蛋白及mRNA表达变化,同时应用甲酰胺浸泡法检测大鼠脑内伊文氏蓝(Evans blue,EB)含量。结果大鼠SAH后6 h、12 h组海马ADAMTS-1mRNA及蛋白表达与sham组相比无统计学意义,于出血后24 h表达明显升高,48 h达到高峰,72 h后仍维持在较高水平。脑内伊文氏蓝含量亦于出血后24 h明显升高,48 h达到高峰并于72 h仍维持在较高水平。ADAMTS-1蛋白表达与脑内EB含量成正相关(r=0.936,P=0.014)。结论大鼠SAH后早期脑损伤过程中ADAMTS-l的表达与血脑屏障损伤成正相关,提示ADAMTS-l可能参与SAH后早期脑损伤的病理过程。

The study on the relationship between hippocampal ADAMTS-1 expression and the permeability of blood-brain barrier in early brain injury in rats after subarachnoid hemorrhage

Objective To explore the relationship between the expression of ADAMTS-1in the hippocampus and the permeability of blood-brain barrier and to investigate the role of ADAMTS-1in the early brain injury(EBI) after subarachnoid hemorrhage(SAH).Method Totally 108 adult male SD rats were randomly divided into 2 groups: the sham-operation group and SAH group.The SAH model was induced by injecting 300μl of autologous arterial blood into the subarachnoid space near the circle of Willis via a cannula in an artificial hole between the olfactory bulb and frontal lobe.The expression levels of ADAMTS-1 in the hippocampus were examined at 6,12,24,48 and 72 h following SAH using western-blotting and RT-PCR.The BBB permeability was evaluated by detection of extravasated Evans Blue.Result The expression of ADAMTS-1 increased dramatically at 24 h,reached the peak at 48 h,and still maintained a high level at 72 h following SAH.The contents of EB increased progressively at 24 h,reached the maximum level at 48 h and maintained a high level at 72 h following SAH.The protein expression levels of ADAMTS-1 and the content of brain EB were positively correlated r = 0.936 P = 0.014.Conclusion ADAMTS-1 in the hippocampus of rats after SAH may be involved in the pathological progression of early brain injury.