Effect Of RHuEPO On Experimental Delayed Cerebral Vasospasm Following Subarachnoid Hemorrhage In Rats

ObjectiveSystemic application of recombinant human erythropoietin (rHuEPO) on the inhibition of the delayed cerebral vasospasm after subarachnoid hemorrhage and its related mechanisms. Methods1、Fifty Wistar rats of clean grade were randomly divided into five groups:control group, non-treatment group, SAH group, SAH+rHuEPO group, SAH+placebo group. The SAH model was constructed by autologous blood two-injection into the cisterna magna.2、First7days after injection of blood through the inner canthus vein blood using enzyme-linked immunosorbent assay (ELISA) in serum endothelin-1(ET-1) inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) content.3、The first7days after injection of blood after cardiac perfusion take basilar artery by measuring the basilar arterial cross-sectional area to determine cerebral vasospasm.4、Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) was used to observe the apoptosis of temporal cortex.Results1、The cross-sectional area of basilar artery of SAH group were reduced by45.0% and41.7%(P<0.01) compared with blank group or non-blood injection group. The area of the basilar artery in SAH+rHuEPO group was larger than that in SAH or SAH+placebo group(P<0.01).2、ET-1and eNOS concentrations of SAH group and SAH+placebo group in serum were significantly increased (P<0.01) compared with the blank group and the non-blood injection group, but eNOS concentration was significantly lower (P<0.01). SAH+rHuEPO group compared with the SAH group and SAH+placebo group, serum ET-1and iNOS concentration were significantly lower (P<0.01) concentration of eNOS was significantly increased (P<0.01).3、The temporal cortex neurons of SAH group and SAH+placebo were loose structured, reduced he number of neurons, disordered arrangement, nuclei stained deep and pyknotic, the nucleolus disappears. These changes in the SAH+rHuEPO group was significantly weakened. The neuronal apoptosis index of SAH group and SAH+placebo were lower than the SAH group and SAH+placebo group (P<0.01). Positive staining neurons were found few in control group and non-blood injection group. Conclusion1、Systemic use of rHuEPO in early stages can be effective prevention of delayed cerebral vasospasm following SAH.2、The mechanism of rHuEPO prevent delayed cerebral vasospasm after SAH may be related to the inhibition of ET-1expression and regulation of NO by regulating iNOS and eNOS expression.3、Systemic use of rHuEPO in early stages has a significant role in cerebral protection in rats after SAH, the mechanism is not only because of reducing cerebral ischemia, but also related to reduce expression of iNOS and thus inhibit NO excessive synthesis.