Tacrolimus (FK506) limits accumulation of granulocytes and platelets and protects against brain damage after transient focal cerebral ischemia in rat
Tacrolimus (FK506) limits accumulation of granulocytes and platelets and protects against brain damage after transient focal cerebral ischemia in rat
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DOI：
10.1248/bpb.30.313
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发表时间：
2007-02-01
影响因子：
2
通讯作者：
Yanagihara, Takehiko
中科院分区：
文献类型：
--
作者：
Noto, Takahisa;Furuichi, Yasuhisa;Yanagihara, Takehiko
采用大鼠大脑中动脉（MCA）闭塞60 min，造成短暂性局灶性脑缺血再灌注损伤，观察他克莫司（FK 506）对脑缺血再灌注损伤的保护作用。MCA闭塞后9 h在大脑皮质观察到MAP 2免疫反应性降低的神经元损伤，并在24 h进一步扩大。在MCA闭塞后9 h和24 h，还观察到用2-硝基咪唑（缺氧标记物（hypoxyprobe-1））的免疫组织化学反应可视化的缺氧区域以及粒细胞和血小板的积聚。他克莫司（1 mg/kg，静脉注射），MCA闭塞后立即给药，减轻皮质损伤，减少hypoxyprobe-1阳性面积，以及MCA闭塞后24小时粒细胞和血小板的数量。免疫组织化学分析显示，他克莫司减少ICAM-1，E-选择素和P-选择素阳性染色的血管数量。这些结果表明，他克莫司通过抑制粘附分子的表达来限制粒细胞和血小板与血管的粘附，并保护神经组织免受缺氧损伤。
We investigated the neuroprotective effect of tacrolimus (FK506) on the ischemia-reperfusion injury caused by transient focal brain ischemia induced by middle cerebral artery (MCA) occlusion for 60 min in rats. Neuronal damage visualized as a decrease of MAP2 immunoreactivity was observed in the cerebral cortex at 9 h after MCA occlusion and further expanded at 24 h. Hypoxic areas visualized with an immunohistochemical reaction for 2-nitroimidazole, a hypoxia marker (hypoxyprobe-1), and accumulation of granulocytes and platelets were also observed at 9 h and 24 h after MCA occlusion. Tacrolimus (1 mg/kg, i.v.), administered immediately after MCA occlusion, attenuated cortical damage and decreased the hypoxyprobe-1 positive area, as well as the number of granulocytes and platelets at 24 h after MCA occlusion. Immumohistochemical analysis showed that tacrolimus reduced the number of blood vessels positively stained for ICAM-1, E-selectin and P-selection. These results suggested that tacrolimus limited attachment of granulocytes and platelets to blood vessels by inhibiting the expression of adhesion molecules and protected neuronal tissue from hypoxic insults.