Effect Of Peroxisome Proliferator-Activated Receptor-Gamma Agonist On The Expression Of Monocyte Chemotactic Protein-1 In Early Diabetic Rats

Objective:To investigate the protection effect and its mechanisms of exogenous peroxisome proliferator-activated receptor-gamma agonist on early diabetic retinopathy by establishing animal model of diabetic rats, and giving rosiglitazone to interfering in model rats and observing the change of expression of serum and retinal monocyte chemotactic protein-1 and pathological damage of retinal capillary. Methods:Intraperitoneal injecting streptozotocin was used for preparing diabetic animal model. Ninety healthy male Wistar rats were randomly divided into 3 groups:normal control group(C group, n=30), blank control of diabetic model group(D group, n=30), rosiglitazone intervention of diabetic model group(R group, n=30). Diabetic model groups were intragastric administrating rosiglitazone with 3mg/kg every day, normal control groups and blank control of diabetic model groups were intragastric administrating saline with equal doses. The body weight and the fasting blood glucose of all rats were detected twice a week. All rats were respectively collected blood and eye specimen after 4 weeks,8 weeks and 12 weeks; Retinal digestive stretched preparation were used for observing retinal vascular form.and count endothelial cells and pericapillary cells; Immunohistochemistry were used for counting positive cells of and monocyte chemoattractant protein-1 on retina; Evans blue were used for detecting the permeability of the blood-retina barrier and enzyme linked immunosorbent assay were used for detecting the expression of MCP-1 in serum. Result:1. In each time point, the body weight of group D and R were obviously lower than group C; the fasting blood glucose of group D and R were obviously higher than group C(P<0.01).2. As compared with group C, the body weight of group D were reduced, the permeability of the blood-retinal barrier were up-regulated, the expression of MCP-1 in serum and retina were up-regulated from 4 weeks. The pericapillary cells were reduced and endothelial cells were increased from 8 weeks. There was significant difference in statistics(P<0.01);As time went on, pathological damage of retinal capillary became more and more serious. There was significant time dependence.3. After the intervention of rosiglitazone, pathological damage of retinal capillary was obviously reduced. As compared with group D, the body weight of group R were increased, the permeability of the blood-retinal barrier were down-regulated, the expression of MCP-1 in serum and retina were down-regulated from 4 weeks. The pericapillary cells were increased and endothelial cells were decreased from 8 weeks. The longer intervention time was, the lighter pathological change of retinal capillary was. There was significant time dependence. Conclusion:1. There was a little MCP-1 expression in the normal rats serum and retina.2. Rosiglitazone can protect early diabetic retinopathy, and may become a new target for preventing and treating DR by activating PPAR-y and down-regulating the expression of MCP-1.3. Diabetic animal model can be successfully induced by intraperitoneal injecting streptozotocin, the method is Convenient with typical model and high success rate, mortality rate is low.