Lipoxin A4 methyl ester protects brain against focal cerebral ischemia reperfusion: Involvement of attenuating the inflammatory response
尚游1 叶习红1 郭培培1 王洁1 袁世荧1 姚尚龙1
Department of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Aim To explore the neuroprotective effects of Lipoxin A4 methyl ester (LXA4 ME) on ischemic brain and discover its underlying mechanisms.
Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h. Intracerebroventricular administration of LXA4 ME immediately after onset of ischemia. Neurological deficits, infarct volume, were assessed. Neuron apoptosis was detected by TUNEL Assay. Myeloperoxidase activity, malondialdehyde level, IL-1β, TNF-α, IL-10 and TGF-β1 were measured in ischemic brain tissue homogenates. NF-κΒ was detected by western blot and electrophoretic mobility shift assay (EMSA).
Results LXA4 ME ameliorated neurological dysfunctions, reduced infarction volume and attenuated neuronal apoptosis. Moreover, Treatment with LXA4 ME suppressed neutrophils infiltration and lipid peroxidation levels; inhibited the activation of microglia and astrocytes; reduced the expression of pro-inflammatory cytokines TNF-α and IL-1β; and up-regulated the expression of anti-inflammatory cytokines IL-10 and TGF-β1 in the ischemic brain. In addition, activation of NF-κΒ was inhibited by LXA4 ME treatment.
Conclusion These results demonstrate that treatment of LXA4 ME affords strong neuroprotective effect against cerebral ischemia reperfusion injury, and that these effects might be associated with its anti-inflammatory property.
