Effect Of EGFR-TKI On Axonal Regeneration Of Rabbit Facial Nerve In Regeneration Chamber: An Experimental Study

Objective To evaluate the effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) on nerve regeneration of facial nerve injury and to provide the theory basis for treatment of peripheral nerve injuries.Methods Twenty rabbits were randomizely divided into 2 groups received a neurotomy to bilateral facial nerves, then the broken nerves were reconnected with silicon tube to make regeneration chamber. The regeneration chamber was filled with either normal saline or 10μg/ml EGFR-TKI .Local immunoreaction , histological changes and electrophysiology were observed at designateive time after neurotomy by Immunity fluorescence,. Electron microscope and Neuroelectricity physiology.Results (1) When 4 weeks postoperation two groups may see that in the regeneration chamber nerve connect the broken ends of fractured bone with the fiber. And the regeneration nerve diameter is 1 . 52±0 . 11mm in the experimental group and 1.01±0.13mm in the control group . When 6 weeks it is 2.18±0.16mm and 1 . 72±0 . 11mm. The difference has the remarkable significance (P<0. 01). (2) Neuroelectricity physiology examination: According to the action potential of the nerve cord to determine the latency period to figure out the nerve conduction speed. When 4 weeks postoperation nerve conduction speed is 0.30±0.03μm in the experimental group, 0.47±0.02μm in the control group. When 6 weeks postoperation it is separately 20.18±1.6m/s and 17.42±1.1 m/s . The difference has the remarkable significance (P<0. 01). (3) HE dyeing and tricolor dyeing: When 4 weeks postoperation the regeneration nerve diameter is 1083±463 in the experimental group and 677±263 in the control group. When 6 weeks it is 1847±512 in the experimental group and 958±437 in the control group. The difference has the remarkable significance (P<0. 01). The tricolor dyeing demonstrate experimental group massive regeneration nerve fibrous bundle, but the control group the few collagenous fibre. (4) Immunity fluorescence examination: Regenerates facial nerve express GAP-43 partly: Two groups when 4 weeks GAP-43 all assumes the positive express, but in the experimental group GAP-43 expresses obviously stronger than in the control group. (5) Electron microscope observation: When 4 weeks postoperation the thickness of the regenerates nerve fibermyelin sheath is 0.30±0.03μm in the experimental group, 0.47±0.02μm in the control group .When 6 weeks postoperation it is separately 0.54±0.04μm and 0.68±0.04μm. The difference has the remarkable significance(P<0. 05).Conclusion:1. EGFR-TKI through the rabbit facial nerve regeneration chamber, may to myelinated axon, the regeneration nerve diameter and the thickness of the regenerates nerve fibermyelin sheath of the damaged facial nerve has the promoter action.2. EGFR-TKI through the rabbit facial nerve regeneration chamber might control the local microenvironment of the regeneration nerve actively and promote conduction velocity of the damaged facial nerve .3. Local administration of EGFR-TKI may accelerate nerve function restore and promote nerve growth. It provide the theory basis for the treatment of the damaged facial nerve on clinic.