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Study of Peroxisome Proliferator-activated Receptor-gamma Excitomotor on Treatment of Retinopathy in Diabetic Rats

Author: GouWenJun
Tutor: LvHongBin
School: Luzhou Medical College
Course: Ophthalmology
Keywords: Peroxisome proliferator- activated receptor -γ agonists Diabetic retinopathy NF-κB Apoptosis
CLC: R774.1
Type: Master's thesis
Year: 2011
Downloads: 16
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Abstract


Objective: To observe the peroxisome proliferator-activated receptor-γ (peroxisome proliferator-activated receptor-γ, PPAR-γ) agonist rosiglitazone (Rosiglitazone) of streptozotocin (streptozotocin, STZ)-induced the Early Diabetic retinopathy (diabetic retinopathy, DR) expression of nuclear factor-κB (nuclear factor kappa B, NF-κB) in the rat retina and retinal ganglion cells (retinal ganglion cells, RGCs) apoptosis, thereby clarify the role of PPAR-γ agonist DR protection, from the molecular level to provide a new idea for the prevention and early treatment of DR. Methods: 90 healthy male Wistar rats (180 ~ 200g) were randomly divided into three groups: normal control group (C), DR Rosiglitazone is group and DR group, each group of rats 30. Further observed 10 rats each group of rats were divided into 4w, 8w and 12w three time points were observed at each time point. Single intraperitoneal injection of 50mg/kg STZ established rat model of diabetes (diabetes mellitus, DM), 72h after tail vein to measure blood sugar, fasting glucose 16.7mmol / L considered successful modeling. Three days after the the DM model into a mold, DR Rosiglitazone is rats given daily rosiglitazone 3mg/kg orally, C group and DR group given daily volume of 0.9% NS gavage. Respectively, after administration 4w, 8w 12w rats in each group were sacrificed, blood sugar and body weight of each group were measured prior to sacrifice, then the removal of the eye, excluding the cornea and lens made eye cup (the the vitreous very few) of the rats, making paraffin sections, HE staining the rat retina organizational structure, using immunohistochemical methods to detect the expression of NF-κB p65 protein in the rat retina, using terminal deoxynucleotidyl transferase-mediated nick end tag (TUNEL) assay the rat retinal RGCs apoptosis index (apoptosis index, AI). Each index are adopted as mean ± standard differential (x ˉ ± s) said, multiple sets of number comparison using single-factor analysis of variance between groups multiple comparison using q test (Student-Newman-Keuls) Act, to P lt; 0.05 statistically significant. Results: (1) Morphological observation of rat retinal tissue: observed by HE staining groups of rat retinal tissue The C rats retinal tissue in the light microscope, divided into 10 layers, layers arranged in an orderly, structured cells in the layers are complete without edema, RGCs no dissolved; DM rat retinal tissue layers disorganized, loose, disorganized, and cells in the layers and the emergence of cell edema, swelling, and found in the retinal ganglion cell layer Some RGCs dissolved. (2) determination of DM into a mold after 4w, 8w, 12w different point in time the blood sugar and body weight of rats: DR group and DR Rosiglitazone blood glucose water were significantly higher than in group C (P lt; 0.01); while DR a slight decrease the the Rosiglitazone group of blood glucose than the DR group, but the difference was not statistically significance (P gt; 0.05). DR the group DR Rosiglitazone rats body weight than those in group C lower (P lt; 0.05); DR Rosiglitazone rats body weight compared with the DR group, the difference was not statistically significance (P gt; 0.05). (3) detection 4w, 8w and 12w at different time points in each group rat retina NF-κB p65 expression: C rats in the experiment at each time point, the expression of NF-κB p65 weak or no expression in the retina; in the DR course of the disease 4w, 8w, and 12w at different time points, NF-κB p65 expression in DR rats retinal integrated optical density (Integral optical density, IOD) values ??were 35.62 ± 2.99,67.59 ± 2.23 and 85.62 ± 3.55, DR Rosiglitazone is group IOD of NF-κB p65 expression in the rat retina were 33.94 ± 2.40,59.58 ± 1.06 and 73.74 ± 2.32. Compared with group C, the DR group and DR Rosiglitazone group rat retina, NF-κB p65 expression was significantly enhanced (P lt; 0.01), and the change was time-dependent; DR Rosiglitazone is group 8w and 12w, large the mouse retina NF-κB p65 expression compared with the same point in time in the DR group was significantly lower (P lt; 0.01), DR Rosiglitazone group 4w when rat retina, NF-κB p65 expression compared to the same point in time DR group not changed significantly (P gt; 0.05); (4) observed 4w, 8w, 12w different time points in each group on rat retinal RGCs apoptosis index: C rats in the experiment at each time point no apoptotic RGCs only see a small amount of RGCs apoptosis; as the duration of the extension, the the DR rats RGCs apoptotic index gradually increased, 4w, 8w, and 12w RGCs apoptosis index (11.00 ± 1.24)%, (27.98 ± 1.71)% and (42.86 ± 1.71)%, significantly higher than that in group C (P lt; 0.01); DR Rosiglitazone is rats 4w, 8w and 12w RGCs apoptosis index (5.32 ± 0.95) %, (16.92 ± 1.35)% and (23.64 ± 1.12)%, significantly higher than that in group C (P lt; 0.01), but compared with the DR group was significantly lower (P lt; 0.01), and with the administration time extend further reduce the apoptotic index. Conclusion: (1) the application of STZ-induced DM rat model is widely recognized as a classic animal model for the study of DR. (2) exogenous PPAR-γ agonist rosiglitazone may by NF-κB expression thereby inhibiting apoptosis of the DR rat retinal RGCs, has a protective effect of early DR rat retina, it is expected to become the DR. new treatment.

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CLC: > Medicine, health > Ophthalmology > Retina and optic nerve diseases > Retinal disease
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