Effects of 5-lipoxygenase inhibitor zileuton on destruction of blood-brain barrier permeability induced by focal cerebral ischemia-reperfusion injury in rats

AIM: To investigate the influential factors of the blood-brain barrier (BBB) permeability and to observe the effects of zileuton, a selective 5-lipoxygenase inhibitor (5-LO), on focal cerebral ischemia-reperfusion injury (CIRI).METHODS: The right middle cerebral artery of the rat was occluded by inserting a thread through internal carotid artery for 2 h, and then reperfused for 24 h. Zileuton (10, 50 mg·kg-1, po) was orally administered 2 h before ischemia and at 0, 5, 10 h after reperfusion. The permeability of blood brain barrier (BBB) was detected by using Evans blue (EB) as a labelling compound. The degree of cerebral edema was estimated by AutoCAD image analysis software. The mRNA of cysteiny leukotrienes receptor1 (CysLTR1) was detected by RT-PCR. The content of LTB4 in serum was measured by enzyme linked immunosorbent assay (ELISA). The expressions of AQP4 and MMP-9 proteins were measured by immunohistochemical staining method. RESULTS: After middle cerebral artery occlussion 2 h/reperfusion 24 h, the permeability of BBB in the brain tissue of injured side and the brain edema degree were increased. The content of LTB4 in serum was elevated. The expression of CysLTR1 mRNA from the brain tissue of occluded side was enhanced. The expressions of MMP-9 and AQP4 proteins of the ischemia realm and ischemia penumbra (IP) of the infarct focus perimeter were increased. Both 10 and 50 mg·kg-1 doses of zileuton dramatically relieved the BBB permeability destruction and the degree of the brain edema, inhibited the expression of CysLTR1 mRNA in the brain tissue and also reduced the content of LTB4 in serum. The expressions of AQP4 and MMP-9 proteins in the brain tissue were also decreased.CONCLUSION: The permeability of BBB is destroyed after the focal CIRI. The mechanisms of protective effect of zileuton might be attributed to its effects by inhibiting the activation of 5-LO pathways on the brain tissue and circulatory blood, reducing the expressions of AQP4 and MMP-9 proteins of the ischemia and IP realm in the brain tissue.