| Objective:(1) Use fluid percussion brain injury device(FPI) to found a standard animal model of optic nerve injury of rabbits and detect the characteristic of this animal model.(2)To investigate the rule of inhibition about the apoptosis of retinal ganglion cells(RGCs) by caspase-3 inhibitor Z-DEVD-FMK after optic nerve injury in rabbits.(3)To investigate the repairment of optic nerve by caspase-3 inhibitor after optic nerve crush in rabbits through two methods:vitreous and periglomerular injection.Methods:Experiment group was dedived into vitreous group and periglomerular group.Each group was 48 rabbits,Vitreous group of the right eye of each rabbit was caspase-3 inhibitor injection group(A group),left eye was the vitreous cavity DMSO injection group(B group).Perbulbar group in the eye of each rabbit's right eye was the perbulbar caspase-3 inhibitor group(C group),left eye was perbulbar injection DMSO group(D group).The rest 8 rabbits were as normal control group.The experiment group was divided into 6 sub-groups by the time of 1,4,7,10,14,21 days after injury with 8 rats in each groups.The animal model of optic nerve injury in rabbits was built by fluid percussion brain injury device(FPI).Based on the preceding research results,caspase-3 inhibitor was injected into the eyes of the vitrous group or periglomerular group,30 minutes after the foundation of animal model of optic nerve injury.Flash-visual evoked potential(F-VEP)and magnetic resonance imaging(MRI)were used to check the varience of the optic nerve injury by the time of 1,4,7,10,14,21 days after optic nerve injury.And according to preceding time point using TUNEL to detect the apoptosis of retinal ganglion cells.Results:(1) F - VEP:Compared with the F - VEP of normal group,the latency of F-VEP in control group rabbits increased gradually,and the amplitude of F-VEP decreased gradually by the time of 1,4,7days after injury(P＜0.05).And keeps stable on day 10.The latency of F-VEP in experiment group increased gradually by the time of 1, 4days after injury,but the latency of F-VEP in experiment group by the time of 4days after injury were significant(P＜0.05)compared with that of control group.The latency of F-VEP in experiment group rabbits decreased significantly,and the amplitude of F-VEP increased significantly by the time of 7,10,14,21days(P＜0.05) compared with that of control group.The latency and amplitude of A group 21 days after injury were 65.46±6.97mv and 6.75±2.75mv,and is statistically significant compared with the C group(latency and amplitude were 72.06±6.57mv and 6.02±1.98mv)(P＜0.05).(2) The MRI of orbit:The MRI of optic nerve in experiment group found the intumescent optic nerve was becoming recovered at the 7th day after optic nerve cruch.The edema around the injuried optic nerve was completely obsorbed between 14-21days.And the morphological changes of optic nerve gradually became normal in 14-21days,meanwhile the high signal around the injuried optic nerve and disordered structure of fossa orbitalis was also be seen in control group.(3)TUNEL:The apoptosis of RGCs could be observed on day 1 after injury, increased at the 4th day,and reached to a climax at the 7th day in control group.Manipulus apoptosis of RGCs were found at 4-10 days after injury in experiment group.And the apoptotic index in RGCs was decreased significantly compared with control group from 4 days after injury(P＜0.05).Vitreous injection of caspase-3 inhibitor Z-DEVD-FMK were statistically significantcompared with that of periglomerular injection at 14-21 days(P＜0.05).Conclusion:(1) We use FPI found a standard animal model of optic nerve injury of rabbits.This model simulates the trauma in clinic,and has a good stability, repeatability,and also is easy to be graded and be operated.As a result,it is an ideal model for the study on the repair mechanism and the treatment of optic nerve injury; (2) Caspase-3 inhibitor Z-DEVD-FMK plays an important role in the secondary death of RGCs after optic nerve injury,it helps us grasp the changes of the function of the optic nerve after injury,and prepare behind evaluated to provide important basis;(3) Caspase-3 inhibitor Z-DEVD-FMK could effectiveiy inhibit the apoptosis of RGCs after optic nerve injury,increase the survival rates of RGCs and dramatically promote the function of the optic nerve after injury;(4) The protection effect of optic nerve about caspase-3 inhibitor Z-DEVD-FMK provide a reliable basis of drug therapy for patients of optic nerve crush in clinic;(5)The therapy effect on optic nerve injury appears weakerly in time of duration through periglomerular injection than vitreous injection,and vitreous injection has better stability than that of periglomerular injection.
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