Neuroprotective Effects Of Dextromethorphan In Diabetic Retinopathy

Objective: To investigate the effect of Dextromethorphan on the apoptosis of retinal neurons,in diabetic rats,and the potential mechanism thereof.Method: forty-eight adult Sprague Dawley rats randomly divided into normal control group(n=12 D group) and diabetic model group(36 were intraperitoneally injected with streptozotocin). Thirty-six rats were successfully made into diabetic models and randomly divided into diabetes mellitus group(A group), Dextromethorphan 10 mg·kg-1d-1 group(B group) and Dextromethorphan 30 mg·kg-1d-1 group(C 组). The six rats of every group were killed at 4 and 8 week, the expression of Caspase-9/8/3 in retina was studied by immunohistochemistry. Apoptosis of retinal neurons was detected by TUNEL assay.Result: Average optical density value of Caspase-9 in retina.In 4 weeks A group, positive expression of Caspase-9 was found in ganglion cell layer. In 8 weeks A group, positive expression was increased and extended to inner nuclear layer. The trend is consistent between C and A. In C group, the positive expression was less in comparison to that in A and B group in the 4 weeks and 8 weeks(P<0.05). There were no significant difference group A and B(P>0.05).Positive expression of Caspase-9 was not found in retina of D group in the 4 weeks and 8 weeks.Average optical density value of Caspase-8 in retina.In 4 weeks A group, positive expression of Caspase-8 was found in ganglion cell layer. In 8 weeks A group, positive expression was increased and extended to inner nuclear layer. The trend is consistent between C and A. In C group, the positive expression was less in comparison to that in A and B group in the 4 weeks and 8 weeks(P<0.05). There were no significant difference group A and B(P>0.05).Positive expression of Caspase-8 was not found in retina of D group in the 4 weeks and 8 weeks.Average optical density value of Caspase-3 in retina.In 4 weeks A group, positive expression of Caspase-3 was found in ganglion cell layer. In 8 weeks A group, positive expression was increased and extended to inner nuclear layer. The trend is consistent between C and A. In C group, the positive expression was less in comparison to that in A and B group in the 4 weeks and 8 weeks(P<0.05). There were no significant difference group A and B(P>0.05).Positive expression of Caspase-3 was not found in retina of D group in the 4 weeks and 8 weeks. The apoptosis index number of retinal.In 4 weeks A group, positive expression of TUNEL was found in ganglion cell layer. In 8 weeks A group, positive expression was increased and extended to inner nuclear layer. The trend is consistent between C and A. In C group, the positive expression was less in comparison to that in A and B group in the 4 weeks and 8 weeks(P<0.05). There were no significant difference group A and B(P>0.05).Positive expression of TUNEL was not found in retina of D group in the 4 weeks and 8 weeks.Conclusion: In early diabetic rats, Caspase-9,Caspase-8 and Caspase-3 could play a role in the development of diabetic retinopathy. Dextromethorphan can decrease the actviton of Caspase-9,Caspase-8,Caspase-3 and apoptosis of retinal neurons to protect neurons in diabetic rats,which has certain therapeutic effect on diabetic retinopathy.