RESUMO
Objective To explore the effects of erythropoietin (EPO) on the expression of signal transducer and activator of transcription (STAT) 1,phosphorylated STAT1 (P-STAT1),STAT3,P-STAT3 and cell apoptosis in rat models of focal cerebral ischemia-reperfusion.Methods Eighty male SpragueDawley rats were randomly and evenly divided into four groups by completely random design method: shamoperation (group A),cerebral ischemia-reperfusion (group B),cerebral ischemia-reperfusion ± saline (group C) and cerebral ischemia-reperfusion ± EPO (group D).The model of focal cerebral ischemiareperfusion injury was established by blocking the left middle cerebral artery.All rats underwent MRI for the detection of the changes of infarct area between 2 h post ischemia and 24 h of reperfusion.Western blot was used to observe the expression of STAT1,P-STAT1,STAT3,P-STAT3.Terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) was used to evaluate the cell apoptosis including the relative area (ROI area/whole brain area of the same layer × 100％) of abnormal signal region,relative optical density (rOD) and apoptotic index.One-way analysis of variance and q test were used to analyze the data.Results On T2WI imaging,rats in group B and group C presented large hyperintense areas in the cortex and subcortex of left hemispheric ((28.00±4.60)％ and (29.70±4.80)％ respectively).Group D presented less hyperintense areas in the cortex and subcortex of left hemispheric compared with group B and group C ((21.10±2.40) ％; F=11.285,P＜0.01).The expression of STAT1 and STAT3 proteins was not significantly affected by ischemia-reperfusion and EPO intervention compared with normal brain tissue (F=0.806,1.558,both P＞0.05).However,the level of P-STAT1 was low in group A (rOD =0.75±0.13) but increased after cerebral ischemia-reperfusion.Compared with group B and group C,P-STAT1 expression was lower in group D (B-D: 2.08±0.15,2.05±0.16,1.92±0.05; F=3.274,P＞0.05).The level of P-STAT3was also low in group A (rOD=1.02±0.09).Compared with group B and group C,P-STAT3 expression in group D was significandy higher (B-D: 2.22±0.13,2.04±0.14,4.21±0.21 ; F=40.719,P＜0.01).The apoptotic index of group B and group C was (42.00±1.30)％ and (41.20±2.50)％,respectively,which was significantly higher than that of group D ((20.90± 1.46) ％ ; F=378.704,P＜0.01).Conclusion Intraperitoneal injection of EPO can reduce the cerebral ischemic area and the number of apoptotic cells in the ischemic penumbra in rat ischemia-reperfusion models through increasing P-STAT3 and decreasing P-STAT1 levels.
RESUMO
Objective To insestigate the pathophysiological mechanisms of spontaneous transient hyperperfusion after cerebral ischemia-reperfusion in rats.Methods Fifty-two SD rats were randomly allocated into sham-operation(group A),cerebral ischcmia 2-hour(group B), and cerebral ischemia 6-hour(group C)groups.Group B were redivided into 0-,0.5-,1-,2-,4-,6-,and 24-hour subgroups according to the reperfusion time;group C were redivided into 0-,0.5-,1-,2-,and 24-hour subgroups according to the reperfusion time (n=4 in each subgroup). Multislice spiral CT perfusion imaging(CTPI)was performed at different time points after ischemia-reperfusion in each group.After completing the scanning.the rats were sacrificed immediately for optical and electron microscopy examinations.Results In group A,compared to the contralateral sides.there were no significant differences in the relatise value of the cerebral blood flow parameters and the results of optical and electron microscopy in the sham-operated regions. In group B, the relative cerebral blood flow (rCBF) and relative cerebral blood volume (rCBV) in the ischemic core area were increased gradually with the extension of reperfusion time. The relative mean transit time (rMTT) and the relative time to peak (rTTP) were decreased gradually, There were no significant differences compared to group A at 6-hour after reperfusion. The optical and electron microscopy revealed that neuronal density in the ischemic core area in group B were decreased, part of the cell volume enlarged and showed vacuolated changes, and part of the neuronal cell bodies and nuclei shrinked, rCBF in the ischemic core area still maintained lower level with the extension of reperfusion time in group C. The ischemic core area showed the increased transient rCBV and rCBV at 0.5 hour after reperfusion in group B and C. The optical and electron microscopy showed that the ischemic core area presented a large number of necrotic and apoptotic cells, and inflammatory cell infiltration. At 6 hours after reperfusion in group B, the increased blood density was observed under the electron microscope in the ischemic core area, showing capillary engorgement and increased pressure. Conclusions The dynamic changes of CTPI in the process of rat middle cerebral artery occlusion and reperfusion have a certain correlation with the pathological mechanisms of injury. The ultra-early spontaneous and transient hyperperfusion after cerebral ischemia-reperfusion in rats is associated with the transient inflammatory hyperemia after reperfusion injury.