Effect Of Ferulic Acid Thermoreversible Gel On Spinal Cord Injury And Its Mechanism

Objective The purpose of this paper was to prepare a thermoreversible in situ gel including ferulic acid and evaluate its quality, and investigate the effect of the gel on the spinal cord injury and its mechanism.Methods ?The ferulic acid thermoreversible gel was prepared by using poloxamer 407 as the main substrate. In order to filter out the gel formulation with suitable gelation temperature, mechanical strength and good three-dimensional morphology, the gelation temperature, phase transition temperature and steady state viscosity were measured, and the microstructure was observed by scanning electron microscopy.?he spinal cord injury model was established with SD rats.We investigated the therapeutic effect of the thermoreversible in situ gel on spinal cord injury model animal. The sham operation group, the model group, the ferulic acid solution group and the ferulic acid gel group were divided into groups. The rats in each experimental group were subjected to motor function scores at Oh,6h, 1d,3d,7d; The T8-T10 segment of the spinal cord were stained with HE staining, immunohistochemistry and Western-Blot detection of multiple related proteins. From the molecular pharmacology level, preliminary reveal the mechanism of ferulic acid hydrogel improving spinal cord injury.Results ?The gelation temperature of the gel prepared in this experiment was 37?, and the poloxamer 407 concentration in the gel was 17%. It had a suitable mechanical strength and modulus of elasticity, SEM observation of the gel was porous three-dimensional network structure,so it could be used as in situ injection.?The established spinal cord injury model of SD rats was simple, stable and reliable, the model rate was nearly 100%. This provided a platform for the follow-up study of spinal cord injury in situ injection therapy.?The gel group showed a good therapeutic effect on spinal cord injury.The recovery of motor function of the gel group was the best; HE staining results demonstrated that ferulic acid hydrogel could significantly improve spinal cord injury in pathology; The expression of LC3, Beclin-1 protein was detected by immunohistochemistry,and the expression of LC3, Beclin-1, Bcl-2 and Bax proteins were detected by Western Blot. It was proved that the administration of the thermoreversible in situ gel could improve spinal cord injury,and it revealed the treatment of spinal cord injury and autophagy-related mechanisms of apoptosis from the molecular level.Conclusion This study shows that ferulic acid hydrogel can significantly enhance the role of ferulic acid in the treatment of spinal cord injury. The Poloxamer 407 hydrogel drug-containing ferulic acid in the protection of its activityat the same time also play a skeleton supporting role. Combine with in situ injection of the way to achieve the local long-acting ferulic acid release, effectively improving the treatment of ferulic acid on spinal cord injury. It overcomes the current bottleneck of poor stability, low bioavailability and short duration of local administration of ferulic acid, and provides a new strategy for efficient treatment of spinal cord injury.