Effect of recombinant human erythropoietin on expressions of matrix metalloproteinase-9 and BCL-2 in the cerebal cortex after occlusion/reperfusion in rats / 国际脑血管病杂志

ABSTRACT

Objective To investigate the possible mechanism of recombinant human erythropoietin (rhEPO) neuroprotection by studying the effect of rhEPO on expressions of matrix metalloproteinase-9 (MMP-9) and BCL-2 following focal cerebral ischemia-reperfusion in rats. Methods A rat middle cerebral artery occlusion/reperfusion (MCAO/R) model was induced by the intraluminal filament method, and intraperitoneal injection of rhEPO was used for intervention. Histopathological changes were observed by HE staining, and the expressions of MMP-9 and BCL-2 in the cerebral cortex of ischemic side were detected with immunohisto-chemistry. Results HE staining At all time points, the numbers of surviving nerve cells were significantly higher in the rhEPO group, and their injury degree was significantly lower. MMP-9 immunohistochemistry staining The positive cells were observed occasionally in the normal control group and the sham-operation group; the MMP-9 positive cells at the ischemic side of brain tissue in a normal saline control group began to appear at 6 hours after reperfusion, it reached the peak at 24 hours and began to decrease at 72 hours; the change trend of MMP-9 positive cells in the rhEPO group was similar to that in the normal saline control group, but it was significantly lower than that in the normal saline control group at the same time points (t were 12. 023 6, 12. 635 0, 12. 779 6, respectively, all P <0. 01). BCL-2 immunohistochemistry staining No positive cells were found in the normal control group and sham-operation group. The numbers of BCL-2 positive cells reached the peak at the ischemic side of brain tissue in the normal saline control group at 6 hours after reperfusion, it reached the peak at 24 hours and further decreased at 72 hours; the change trend of BCL-2 positive cells in the rhEPO group was similar to that in the normal saline control group, but it was significantly higher than that in the normal saline control group at the same time points (t were 5. 763 1,8. 110 1, and 5. 798 7, respectively, all P <0. 01). Conclusions rhEPO may inhibit cortical neuronal apop-tosis at the ischemic side by inhibiting MMP-9 expression and up-regulating BCL-2 expression so as to play a neuroprotective effect.