The Neuroprotective Effect Of Emodin On Spinal Cord Injury In Rats

Objective:1?To investigate the effect of emodin on motor function recovery after acute spinal cord injury?SCI?in rats.2?To investigate the effect of emodin on spinal cord edema induced by acute spinal cord injury?SCI?and its mechanism.3?To investigate the effects of emodin on oxidative stress and inflammatory response in rats after acute spinal cord injury?SCI?.Methods:345 healthy female Sprague-Dawley rats in SPF were randomly divided into five groups:sham group?group A?,model group?group B?,low-dose group,middle-dose group and high-dose group of emodin?groups C?D?E?,n=69.Rat models of SCI were established by using the modified Allen's method.?1?Functional recovery was evaluated using the Basso–Beattie–Bresnahan?BBB?scale and inclined plate test on the 3^rd?7^th?14^thh and 28^thh day after SCI.?2?On the 3^rd day after SCI,The pathological changes of the spinal cord was observed by hematoxylin-eosin?HE?staining;The water content of spinal cord was detected by dry-wet weight method;The blood-spinal cord barrier?BSCB?permeability was detected by Evans blue;TheexpressionsofAquaporin-4?AQP-4?andMatrix metalloproteinase-2?MMP-2?mRNA and protein were detected by RT-PCR and Western blot respectively.?3?On the 7^th day after SCI,Neuron Nylon Body was observed with Toluidine blue staining;The changes of myelinated nerve fibers were observed by transmission electron microscope?TEM?;Nrf2?HO-1?NQO1?GFAP?NF-?B protein were detected by Western Blot;The content of TNF-??IL-1??IL-6 were detected by ELISA;Immunofluorescence staining was performed to observe the expression of the GFAP?NG2 and ED-1.Results:?1?The BBB and inclined plate scores in groups C?D?E on the 7^th?14^th and 28^thh day after SCI were higher than that in group B?P<0.05?,and the group E was the best?P<0.05?;?2?On the 3^rdd day after SCI,HE staining showed that there was a large hemorrhage in the section of group B,the nerve cells were swollen and damaged,and a large number of inflammatory cells were infiltrated,the tissue gap was widened and the edema was severe,groups C?D and E of the above pathological changes were better than group B,and among them,group E improved the most.The spinal cord water content,there were significant difference between group B and groups D?E,and in groups C?D and E.The Evans blue content in groups C?D and E were lower than that in group B?P<0.05?.The expressions of AQP-4 and MMP-2 m RNA and protein in groups C?D and E were lower than that in group B?P<0.05?,but no significant differences was found between groups C and D of the expression of MMP-2 mRNA?P>0.05?.?3?On the 7^th day,Nylon Body of group B and C started to fuse,the fusion of group D and E were significantly alleviated than group B and C;Transmission electron microscope showed that the changes of demyelination were obvious in group B and C,group D and E were Significantly improved than group B and C;Western Blot showed that Nrf2?HO-1?GFAP?NF-?B protein expression,groups C?D and E compared with group B,NQO1 protein expression,groups D and E compared with group B,and the difference was statistically significant?P<0.05?;ELISA showed that the content of TNF-??IL-6,groups C?D?E compared with group B,the content of IL-1?,group D and E compared with group B,and the difference was statistically significant?P<0.05?;Immunofluorescenceshowed that the expressions of GFAP and NG2 in groups C?D and E were higher than that in group B,and the groups D and E were more obvious;The expression of ED-1 in groups C?D and E were decreased significantly compared with group B.Conclusion:1?Emodin can promote the recovery of limb function after SCI in rats.2?Emodin can alleviate spinal cord edema,which could be correlated with the down-regulated expressions of AQP-4 and MMP-2,and reduced the permeability of BSCB.3?Emodin has protective effect on neurons after SCI.The mechanism may connect with activating Nrf2-ARE pathway,reducing the expression of NF-?B?ED-1?TNF-??IL-1??IL-6,and promoting the expression of GFAP and NG2.