The Regulatory Effects Of Donepezil Hydrochloride On The Expression Of Bcl-2/Bax MRNA In Rat Retina Following Eye Contusion

Objectives:Contusion of retina is a common cause of ocular trauma either in normal time or in wartime.Compared with anterior ocular injury,retinal injury is more complicated,hard to early detect as well as treat in clinical practice which often leads to visual deterioration or even blindness.The key point in the treatment of retinal contusion is early diagnosis so as to inhibit the delayed neural damage and promote regenerations of axons.Loss of the retinal components may involve the apoptosis of retinal neurons.Bcl-2/ Bax is recognized as important genes in regulating apoptosis.Donepezil hydrochloride,used for Alzheimer disease(AD),is a second generation inhibitor of cholinesterase.Recent studies have shown the protective effect of donepezil hydrochloride on hippocampus in rats in the existence of glutamate or in ischema-reperfusion injury. Someone has reported this protective effect on retinal ganglion cells in vitro and vivo.Our study is to successfully establish a retinal bruise model and observe the transcription and changes of Bcl-2 / Bax so as to clarify the mechanism of donepezil hydrochloride,thus provide new approach for future treatment.Methods:24 female Sprague-Dawley(SD) rats were randomly assigned to 3 groups:normal control group(group A),donepezil hydrochloride administrated group(group B) and distilled water group(group C).In the group B:Donepezil was freshly dissolved in distilled water at a concentration of 1g/l.The drug was orally administered by gavage twice daily in a volume of 5 ml/kg(5 mg/kg) in 8 animals for 7 days starting 1 day after retinal bruise model was successfully induced.In the group C,the same volume of distilled water was orally administered twice daily in 8 animals for 7 days.In group B and group C,all models were made by modified Allen'S falling strike.Bcl-2 mRNA and Bax mRNA were examined by RT-QPCR on the 8th day.Results:1.Expression of Bcl-2 mRNA in all groups:Transcriptional quantity of Bcl-2 in group A is the highest.Transcriptional quantity of Bcl-2 in group B is 0.63 time that of group A,while group C is 0.56.There is statistical difference between group A and group B(P＜0.01).There is statistical difference between group B and group C(P＜0.05).2.Expression of Bax mRNA in all groups:Transcriptional quantity of Bax in group A is the lowest.Transcriptional quantity of Bax in group B is 2.99 time that of group A,while group C is 3.23.There is statistical difference between group A and group B(P＜0.01).There is statistical difference between group B and group C(P＜0.05)Conclusions:Donepezil hydrochloride has an important role in regulating expression of Bcl-2/ Bax,that is,donepezil hydrochloride promote the expression of Bcl-2,but inhibit the expression of Bax.Our study also certify that donepezil hydrochloride administrated by mouth instead of repeated vitreous injection has a protective effect on retinal survival without any serious adverse effect.This study indicated that donepezil hydrochloride could be considered as an ideal medicine for neural protection after retinal bruise.