ATP Promotes The Repair Of Spinal Cord Injury By Activating The Akt/mTOR/STAT3 Signal Transduction Pathway In Rats

Objective Endogenic neural stem cells (NSCs) can differentiate into neurons leading to the healing of SCI, however, its molecular mechanism is not clear in SCI. In this study, we aimed to investigate the mechanism of ATP-activated serine/threonine-specific protein kinase (Akt)/mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in the physiology and pathology of spinal cord injury (SCI).Methods Adult specific pathogen-free female Sprague-Dawley rats (128) were randomly divided into four groups (n=32):Using a modified Allen's stall to produce model of SCI at T8～10 in rats of group A, B, C. Group A, in which group rats were subjected to the administration of ATP, for 7 days; Group B, in which group rats were subjected to the administration of physiological saline (equal-volume), for 7 days; Group C, in which group rats were subjected to the administration of ATP and rapamycin, for 7 day; Group D, in which group rats were subjected to laminectomy in combination with the administration of physiological saline (equal-volume), for 7 days. Locomotor activitys of rats were evaluated using the Basso, Beattie, and Bresnahan (BBB) rating scale at postoperative 1,2,3,4 weeks. Then, detecting the expressions of spinal cord cell marker [Nestin, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP)] and the mTOR pathway factors (Akt, mTOR, STAT3) in all of groups at postoperative 1,2,3,4 weeks by Immunohistochemistry analysis, Western blotting assay and real time RT-PCR analysis.Results The BBB scores of rats in group A showed a steady increase in postoperative 1～4 weeks and were all significantly higher compared with that found in group B and C, but were less than that of group D (P<0.05). Analyzing Immunohistochemistry, Western blotting, real time RT-PCR results, in postoperative 1～4 weeks, the expression of Akt, mTOR, STAT3, NSE in rats of group A showed a steady increase, however, Nestin was gradually decreased, which were all significantly higher than that of group B, C, D (P< 0.05); The expression of GFAP showed a steady increase in group A and were all significantly less than that of group B and C, but were higher that of group D (P< 0.05). The differences of expression of each indicator between in group B and D or group C and D were statistically significant in 1～4 weeks (P< 0.05), the differences of Akt, P-Akt, mTOR, P-mTOR, STAT3, P-STAT3 between in group B and C by Western-blot were significant in 1～4 weeks, the differences of remaining indicator between group B and C in 1～4 weeks were no statistically significant (P>0.05). Conclusion1. ATP promotes the repair of SCI in rats2. ATP can activate the Akt/mTOR/STAT3 pathway in SCI in rats3. ATP-activated Akt/mTOR/STAT3 pathway contribute to the repair of SCI in rats4. ATP can activate the mTOR/STAT3 pathway to induce endogenic NSCs to proliferate and differentiate into neurons in rats, contribute to the healing of SCI.