The Activation Of CAMP/Epac2/Akt Kinase Signaling Pathway Promotes The Repair Of Spinal Cord Injury In Rats

Objective:To investigate the mechanism of cAMP derivative (8-CPT-2’-O-Me-cAMP) activated mammalian Epac2/Akt signal pathway in the physiology and pathology of spinal cord injury(SCI).Methods:Ninety-six adult healthy female Sprague-Dawley rats were randomly divided into4groups(n=24). The rats in groups A, B and C were made the SCI models at by using a modified Allen’s stall. The rats were subjected to the administration of8-CPT-2’-O-Me-cAMP[0.5mg/(kg-d)] for7days in group A, to the administration of10%DMSO (equal-volume) for7days in group B, to the administration of8-CPT-2’-O-Me-cAMP[0.5mg/(kg-d)] and LY294002[0.2mg/(kg-d)] for7days in group C. The rats in groups D were observed as Normal control group. Locomotor activity was evaluated using the BBB rating scale at the postoperative lst.2st,3rd,4th weeks every group. Then,the expressions of spinal cord cell marker (Nestin; glial fibrillary acidic protein, GFAP; NF200)and the pathway factors (Epac2; Akt)were detected at the every weeks by HE staining, immunofluorescence analysis and real-time fluorescence PCR analysis.Results:The BBB scores in group A showed a steady increase in the postoperative1st-4th weeks and were significantly higher than those in groups B and C (P<0.01), but were lower than that in group D (P<0.01). In the postoperative1st-3th weeks, The mRNA expression of Epac2in group A was significantly higher than group B (P<0.01) and group D (P<0.01), but was no different to group C. The mRNA expression of Akt in group A was significantly higher than group B (P<0.01), group C (P<0.01) and D (P<0.01). The mRNA expression of Nestin and NF200in group A were significantly higher than group B, C and D(P<0.01) at1st-4th weeks. There were no different mRNA expression of GFAP between group A, B and C. The similar changes were found by assay of Integrated optical density of immunofluorescence. A lots of cavities were observed in spinal cord tissues by HE staining in group A、B and C.Conclusion:The derivative of cAMP can activate the Epac2/Akt pathway to induce neural stem cells to proliferate and differentiate into neurons and enhances the healing of SCI in rats.