The Effect Of Pyridoxamine On The Retina From Hyperglycemic Memory To Diabetic Retinopathy

ObjectiveTo detect retinal cell apoptosis and the expressions of advancedglycation end products (AGEs) and vascular endothelial growth factor inthe retina of diabetic rats treated with pyridoxamine， to study theprotective effect of pyridoxamine on the retina from hygerglycemicmemory to diabetic retinopathy.Methods6weeks old SD rats (male,200-220g body weight,clean grade) wereassigned to normal or diabetic groups. Diabetes was induced withintraperitoneal injection of streptozotocin (55mg/kg BW). Diabetic ratswere divided at random among4groups: early treatment group (ET group),diabetes treated with pyridoxamine group (PM group), metabolic memorygroup (MM group) and diabetes group (DM group).Normal rats act as NC group; ET group were in good glycemic controlfor the entire duration of the experiment; PM group were allowed to remainin poor glycemic control for8weeks and this was followed by good glycemiccontrol and treated with pyridoxamine intragastric administration（200mg·kg-1·d-1）for8additional weeks. MM group were allowed to remain inpoor glycemic control for8weeks and this was followed by good glycemiccontrol for8additional weeks; DM group were in poor glycemic controlfor the entire duration of the experiment.16weeks later,the rats were killed and the eyeballs were removed．Theretinal ultrastructure of each group rats were observed by light microscopy and electron microscopy. Retinal cell apoptosis was detectedby TdT mediated dUTP nick ending labeling (TUNEL). The expressions ofAGEs in serum and retina were measured by enzyme-linked immunosorbentassay (ELISA). The retina distributions of VEGF were detected byimmunohistochemical method．ResultsCounting nerve cells apoptosis, NC group, ET group, PM group, MM groupand DM group’s apoptotic index was7.23±1.35%，7.42±1.37%,21.86±1.94%,37.36±3.30%，36.45±5.00%respectively. NC group compared withET group were not significantly differential(P﹥0.05), MM group and DMroup were not significantly differential neither(P﹥0.05), but they bothincreased significantly comparing with NC group(P﹤0.05). PM group wassignificantly higher than NC group and ET group (P﹤0.05), and lower thanMM group and DM roup (P<0.05). The content of AGEs in serum and retinalof NC group and ET group were not significantly differential(P﹥0.05),neither MM group and DM group were(P﹥0.05). While PM group wassignificantly higher than NC group and ET group (P﹤0.05), and lower thanMM group and DM roup (P<0.05). The expression of VEGF in retina ofdifferent group rats were detected by immunohistochemical staining, theaverage optical density was7.38±1.52，7.02±1.58,15.41±2.35,27.57±4.24，27.66±5.02respectively. NC group compared with ET group werenot significantly differential(P﹥0.05), MM group and DM roup were notsignificantly differential neither(P﹥0.05), but they both increasedsignificantly comparing with NC group(P﹤0.05). PM group wassignificantly higher than NC group and ET group (P﹤0.05), and lower thanMM group and DM roup (P<0.05). ConclusionsDiabetic rats can be caused the phenomenon of "metabolic memory" ina certain time state of high blood sugar. Hygerglycemic memory play animportant role in the mechanism of diabetic retinopathy. The mechanismthat pyridoxamine protecting the retina from hygerglycemic memory todiabetic retinopathy is not through the hypoglycemic effect, but theinhibition of oxidative stress, to reduce the expressions of AGEs in serumand retina of diabetic rats in the late diabetes．...