胍丁胺对脑缺血再灌注损伤大鼠血脑屏障的作用机制研究

Study on the effect and mechanism of agmatine on blood brain barrier with cerebral ischemic reperfusion injury rats

目的研究胍丁胺对血脑屏障(BBB)通透性的影响及其与水通道蛋白(AQP)的相关性。方法将大鼠随机分为假手术组、实验组和模型组。大脑中动脉栓塞2 h后,实验组和模型组分别腹腔注射胍丁胺(50 mg·kg-1)和等量0.9%Na Cl。通过测定脑水含量、BBB通透性,考察BBB的损害程度,用2,3,5-氯化三苯基四氮唑(TTC)染色法比较梗死灶大小,苏木精-伊红(HE)染色和电镜观察神经元形态学变化,Western-blotting法检测AQP4、AQP9的表达。结果实验组BBB通透性显著下降,变性神经元数明显减少,同时,AQP4与AQP9的表达较模型组显著降低。结论胍丁胺通过降低AQP4、AQP9的表达来改善BBB通透性,从而减轻脑水肿引起的神经元损伤。

Objective To observe the effect of agmatine on brain ede-ma and examine the relation between blood brain barrier （ BBB） per-meability and aquaporin 4 （ AQP4 ） and aquaporin 9 （ AQP9 ） in rats with cerebral ischemic reperfusion.Methods Health male Sprague-Dawley rats were randomly divided into sham group , model group and test （ agmatine ） group.And 2 h after middle cerebral artery occlusion, giving agmatine （ 50 mg · kg -1 ） in test group or 0.9%NaCl in sham and model groups by intraperitoneal injection, respec-tively.Brain edema and the size of the brain infarct were assayed by brain water content and BBB permeability and 2,3,5 -triphenyltet-razoliumchloridstaining（ TTC）.The morphological changes of neurons were observed by hematoxylin and eosin staining and transmission electron microscopy.And the expression of AQP4 and AQP9 were assessed by Western -blotting.Results The BBB permeability de-creased significantly and the morphological changes of neurons were reduced significantly and the expression of AQP4 and AQP9 decreased significantly in rats with agmatine.Conclusion Agmatine reduce the injury of the BBB by decreasing the expression of AQP4 and AQP9 , and relieve the neuron injury induced by brain edema.