Astrocytic effect of low molecular weight heparin-superoxide dismutase conjugate in interleukin-6 overexpressing mice following local cerebral ischemia

摘要

BACKGROUND:Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect. OBJECTIVE:To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6(IL-6) overexpressing mice following local cerebral ischemia. DESIGN,TIME AND SETTING:Randomized,cytological,controlled,animal study was performed in the Department of Physiology and Neuroscience,Neurology and Biochemistry and Molecular Biology,Medical University of South Carolina from January 2005 to March 2005. MATERIALS:Nine IL-6 transgenic mice,irrespective of gender,were randomly divided into three groups:sham-operated,model,and treatment,with three mice in each group.With exception of the sham-operated group,right middle cerebral artery occlusion was induced in the mice. Expression of glial fibrillary acidic protein,an astrocyte marker,was determined by immunohistochemistry.Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute,Shandong University. METHODS:Two minutes prior to ischemia induction,0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxide dismutase conjugate were administrated via the femoral artery in the model group and treatment group,respectively.The sham-operated group underwent the same protocols,with the exception of occlusion and treatment. MAIN OUTCOME MEASURES:The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy(x200). RESULTS:In the sham-operated group,there were a large number of astrocytes in the IL-6 transgenic mice.However,the cell bodies were small,and the branches were few and thin.The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups,the number of astrocytes significantly increased,and the cell body became larger,following treatment with low molecular weight heparin-superoxide dismutase conjugate.Astrocytes exhibited hypertrophy and hyperplasia,and the processes became longer and thicker. CONCLUSION:The low molecular weight heparin-superoxide dismutase conjugate may provide neuroprotection through astrocytic activation at the super-early stage of cerebral ischemia and reperfusion.