| Objective: To investigate the effect of peroxisome proliferator-activated receptor-gamma excitomotor, rosiglitazone, on nuclear factor kappa B expression and apoptosis of the retinal ganglion cells(RGCs) in the retina in diabetic retinopathy(DR) induced by streptozotocin, then set out the protective effect of the PPAR-γagonists on DR from molecular level, and provide a new way for prevention and early treatment DR. Methods: Ninety male Wistar rats were divided into three groups randomly:Normal control group (C group), DR group and DR+Rosiglitazone group, 30 rats in each. Each group was divided into 4weeks, 8weeks and 12weeks of the three time points, 10 rats were observed at each time point. DM models were established by intra-peritoneal injection of 50mg/kg STZ. After 72 hours, blood glucose was measured from tail vein, more than 16.7mmol/L was regarded as successful model. 3mg/kg of rosiglitazone was intragastricly administered once per day in DR+Rosiglitazone group and the same volume of 0.9%N.S was intragastricly administered once per day in control group and DR group after modeling 3 days. After blood glucose and weight was measured at 4 weeks, 8 weeks and 12 weeks, the rats were sacrificed and removed eyeballs to make the eye cups. Structure of retinal layers was observed by hematoxylin-eosin staining. NF-κB p65 protein expression was detected by immunohistochemistry in the retina. The apoptotic index of the retinal ganglion cells was detected by TUNEL. The results were showed by means plus or subtracting standard, the groups means was compared by ONE-WAY AONVA, the deviation of between groups means was compared by Student-Newman-Keuls. The difference of P<0.05 had statistical significance. Results: (1) Morphological of retina in rats: Retina was divided into ten layers under the light microscope, layers arranged in an orderly, the cells of layers of retina were without edema, and RGCs were not solution in C group by hematoxylin-eosin staining. The layers of retina arranged disorderly, the cells of layers were edema, and RGCs were solution in RGC layer of diabetes mellitus rats by hematoxylin-eosin staining. (2) The blood glucose and weight of rats at 4 weeks, 8 weeks and 12 weeks of the time points: The blood glucose level was significantly elevated at various time points in DR group and DR+Rosiglitazone group compared with control group(P<0.01). The blood glucose level was almost same at various time points in DR+Rosiglitazone group compared with DR group (P>0.05). The weight of rats was decreased in DR group and DR+Rosiglitazone group compared with control group (P<0.05). The weight of rats was almost same at various time points in DR+Rosiglitazone group compared with DR group (P>0.05). (3) NF-κB p65 expression in retina of rats: The NF-κB p65 was expressed weakly or was not expressed in rat retina of control group at various time points. At 4 weeks, 8 weeks and 12 weeks of the time points, the value of integral optical density of NF-κB p65 was 35.62±2.99, 67.59±2.23 and 85.62±3.55 in rat retina of DR group. The value of integral optical density of NF-κB p65 was 33.94±2.40, 59.58±1.06 and 73.74±2.32 in rat retina of DR+Rosiglitazone group. DR group and DR+Rosiglitazone group were compared with control group, NF-κB p65 of rat retina expression was elevated significantly (P<0.01), and there was significant time dependence. At 8 weeks and 12 weeks of the time points, DR+Rosiglitazone group was compared with DR group, NF-κB p65 of rat retina expression was lower significantly(P<0.01), but the NF-κB p65 expression was almost same in DR+Rosiglitazone group compared with DR group at 4 weeks(P>0.05). (4) The apoptosis index of RGCs in rat retina: There were few apoptotic cells in rat retina of control group at various time points. The apoptosis index was increased with the extension of course. At 4 weeks, 8 weeks and 12 weeks of the time points, the apoptosis index of retinal ganglion cells was (11.00±1.24)%, (27.98±1.71)% and (42.86±1.71) % in DR group and it was significantly elevated at various time points in DR group compared with control group(P<0.01). The apoptosis index of retinal ganglion cells was (5.32±0.95)%, (16.92±1.35)% and (23.64±1.12)% in DR+Rosiglitazone group. It was significantly elevated at various time points in DR+Rosiglitazone group compared with control group(P<0.01). Compared with DR group, the apoptosis index of DR+Rosiglitazone group was significantly reduced(P<0.01) and it was reduced furtherly with the extension of intervention time. Conclusion: (1) Diabetic rat model as one of the classic animal modeles was copied by STZ, and used to study diabetic retinopathy. (2) Rosiglitazone as one of the Peroxisome proliferator-activated receptor-gamma excitomotores may be used to inhibit apoptosis of RGCs through the expression of NF-κB in rat with diabetic retinopathy. It is expected to become one of the new therapeutic methods because it has protective retina role in rat with DR.
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