Influence of nuclear factor erythroid 2-related factor 2 genotype on tumor necrosis factor-α and metalloproteinase-9 expression in spinal cord after spinal cord injury in mice / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) as a key transcription factor of cytoprotection against inflammation in the spinal cord upregulation of matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α(TNF-α) after spinal cord injury (SCI).</p><p><b>METHODS</b>Wild-type Nrf2(+/+) and Nrf2(-/-)-deficient mice were subjected to a murine SCI model induced by the application of vascular clips (force of 10 g) to the dura after a three-level T8-T10 laminectomy. The wet/dry weight ratio was used to reflect the percentage of water content of impaired spinal cord tissue at 48 h after SCI. The mRNA levels of MMP-9 were determined using reverse-transcriptase polymerase chain reaction (RT-PCR), and the protein levels of TNF-α and MMP-9 were detected by enzyme-linked immunosorbent assay at 24 h after SCI. Furthermore, gelatin zymography analysis was used to show MMP-9 activity of spinal cord tissue at 24 h after SCI. Software SPSS 16.0 was used for the statistical analysis.</p><p><b>RESULTS</b>After SCI, spinal cord water content, the expression of TNF-α and MMP-9 all increased in both injured Nrf2(+/+) and Nrf2(-/-) mice compared with their respective sham-operated mice. However, Nrf2(-/-) mice were shown to have more severe spinal cord edema, more TNF-α expression, more production and activity of MMP-9 compared with their wild-type Nrf2(+/+) counterparts after SCI (P < 0.05).</p><p><b>CONCLUSIONS</b>The results suggest that Nrf2 plays an important protective role in limiting the spinal cord upregulation of TNF-α and MMP-9 after SCI. It may be a new therapeutic target of SCI.</p>

Early systemic administration of erythropoietin partially relieves cerebral vasospasm after subarachnoid hemorrhage in rabbits / 中华神经医学杂志

Objective To study the effect of carry systemic administration of erythropoietin (EPO)on cerebral vasospasm(cvs)after subarachnoid hemorrhage(SAH)and explore the possible mechanism. Methods Thirty male New Zealand rabbits were randomized equally into 5 groups.namely the blank control group, saline group,SAH model group,SAH+placebo group,and SAH+recombinant human erythropoietin(rHuEPO)group.In the latter 3 groups,rabbit SAH model was established by autologous blood injection into the cisterna magna,and in the saline group,only normal saline was injected.Fiveminutes after the blood injeetion,the rabbits received intraperitoneal injection of rHuEPO or placebo(EPO solvent)as indicated,followed by another 5 injections at the interval of8 h.Forty-eighthours after the model establishment,the rabbits were sacrificed by perfusion-fixation and the basiiar army Was taken.The cross-sectional area of the lumen of the basllar artery Was measured to evaluate the degree of cerebral vasospasm.TUNEL assay was used to detect endothelial cell apoptosis in the basilar artery. Results The average cross-sectional area of the basilar arteries showed no significant difference between the blank control and the saline groups or between SAH and SAH+placebo groups(P>0.05).The cross-sectional area of the basilar artery in SAH+rHuEPO group was significantly greater than that in SAH group and SAH+placebo group(P<0.05),but smaller than that in the blank control and saline groups.TUNEL assay revealed less intense apoptosis of the endothelial cells in SAH+rHuEPO group than in SAH group or SAH+placebo group(P0.05).Conclusion Early systemic administration of rHuEPO can decrease endothelial cell apoptosis in the basilar artery and may partially attenuate the intensity of CVS in rabbits with SAH.