Effect And Mechanism Of GW3965/PLGA/Chitosan Compound Drug-carrying Nerve Conduit On Peripheral Nerve Injury Repair

Objective: Peripheral nerve injury is a difficult problem in clinical work,and there are still many shortcomings in current treatment methods.This study aims to explore the effect of LXR agonist GW3965 on peripheral nerve injury and the therapeutic effect of compound drug-carrying nerve conduit on sciatic nerve defect model in rats,so as to provide new ideas for the treatment of peripheral nerve injury.Methods: The experiment was divided into three parts.The first part was in vitro cell experiment.The effect of GW3965 on the proliferation of RSC96 Schwann cells was determined by CCK-8 method.The effect of GW3965 on the secretion of neurotrophic factor in Schwann cells was studied by real-time quantitative PCR,and the inhibitory effect of GW3965 on the inflammatory response of Schwann cells was studied by western blot.The second part was the preparation and characterization test of PLGA microspheres and nerve conduit.PLGA drug-loaded microspheres were prepared by emulsifying solvent volatilization method,chitosan nerve conduit was prepared by leaching method,and their physical characterization characteristics were tested in vitro.The third part was the in vivo animal experiment.The repair effect of GW3965/PLGA/ chitosan compound drug-loaded nerve conduit on peripheral nerve injury in rats was studied by a series of functional and molecular biological methods such as footprint analysis,electrophysiological examination,muscle wet-weight ratio,muscle HE staining,immunofluorescence staining,transmission electron microscopy and so on.Results: GW3965 could promote the proliferation of RSC96 Schwann cells,promote the secretion of neurotrophic factors,reduce the release of inflammatory factors induced by LPS,and play a positive role in nerve regeneration microenvironment.PLGA sustained release microspheres loaded with GW3965 were prepared successfully and their surface characteristics of drug loading were tested.Chitosan nerve conduit was successfully prepared,and its physical properties were tested.It was found that the nerve conduit had good bending resistance and toughness and could resist certain external forces to provide protection and support for nerve growth.Through a series of animal experiments,it was found that the results of GW3965 nerve conduit group,such as footprint analysis,nerve electrophysiology,muscle wet-weight ratio,muscle HE staining,immunofluorescence staining and transmission electron microscopy detection,were superior to those of the nerve conduit control group,and were close to those of the autograft group.GW3965/PLGA/ chitosan compound drug-loaded nerve conduit showed good nerve damage repair effect.Conclusion: LXR agonist GW3965 has a positive effect on the improvement of peripheral nerve regeneration microenvironment,and GW3965/PLGA/chitosan compound drug-loaded nerve conduit has a good effect on nerve injury repair.The research results can provide a new therapeutic strategy for the repair of peripheral nerve injury.