Effects of cetuximab on neuronal apoptosis,glial cell activation and amy-loid precursor protein expression in brain tissue in rats with cerebral is-chemia/reperfusion
Aim:To explore the effects of cetuximab on neuronal apoptosis,glial cell activation,and expression of amy-loid precursor protein(APP)in brain tissue after cerebral ischemia/reperfusion in rats.Methods:A total of 27 SD rats were randomly allocated into sham surgery group,ischemia/reperfusion group,and cetuximab group,with 9 rats in each group.Animal model of the focal cerebral ischemia/reperfusion model was induced by ligating middle cerebral artery,then adminis-tering cetuximab(106 μg/d)through lateral ventricular injection immediately after surgery,lasting for 7 days.Three animals were randomly selected from each group,and neurological function score was assessed on the 3rd and 7th day after surgery.The remaining 6 animals in each group were euthanized on the 3rd and 7th day after ischemia/reperfusion surgery,brain tis-sue was extracted,and the expression of APP and glial fibrillary acidic protein(GFAP)were observed using immunofluores-cence staining.The neuronal apoptosis index was measured using TUNEL staining.Glial cell suspension was prepared by ex-tracting cortical tissue from newborn rats.The glial cells were cultivated in a sugar free and serum free medium and cetux-imab(10 μg/mL)for 2 hours in a hypoxic incubator,and then the cells was replaced the medium with normal sugar/serum and continued to culture in a normal oxygen incubator for 6 hours.Then cells was collected and observed the changes of GFAP fluorescence intensity.The control group did not underwent hypoxia/reoxygenation treatment,and the hypoxia/reoxy-genation group was not added with cetuximab.Results:Compared with the sham surgery group,the ischemia/reperfusion group showed an increase in neurological function score,apoptosis index,GFAP staining of glial cells and expression of APP(P<0.05).Compared withtheischemia/reperfusiongroup,thecetuximabgroupshowedadecreaseofneurologicalfunction score,apoptosis index,GFAP staining and APP expression(P<0.05).Compared with the control group,the GFAP immuno-fluorescence intensity of glial cells in the hypoxia/reoxygenation group increased,which decreased in the cetuximab group compared with the hypoxia/reoxygenation group(P<0.05).Conclusion:Cetuximab could promote the recovery of neuro-logical function in rats with cerebral ischemia/reperfusion,and its mechanism may be related to reducing APP expression,inhibiting neuronal apoptosis and glial cell activation.
万方数据
维普
