Protective effect ofblocking the signal path of p38 mitogen-activated protein kinase on blood-retinal barrierand retinal ganglion cells in early diabetic rats

Abstract

：Objective To investigatethe protective effect of blocking the signal path of p38 mitogen-activated protein kinaseon blood-retinal barrier (BRB) and retinal ganglion cells (RGC) in early diabetic rats.Methods A total of 60 Wistar rats were divided into the control and diabetes group, with30 rats in each group. Diabetes was induced in rats in diabetes group by peritonealinjection of streptozotocin (STZ) ; the plasma glucose level of >16.7 mmol/L indicatedthat the diabetes model was set up successfully. The rats in the control group underwentperitoneal injection of equivalent sodium citrate solution. IgG leakage method was used tomeasure the damage of BRB function and vascular leakage. The expression and localizationof caspase-3 and vascular endothelial growth factor (VEGF) in retina of diabetic rats wereexamined by immunohistochemistry analyses. Two weeks after the establishment of thediabtes model, the rats in diabtes group underwent intravitreal injection with SB203580, ap38 inhibitor; six weeks after the injection, the expression of caspase-3 and VEGF wasdetected, and the number of apoptosis RGC was counted via immunofluorescence technique.Results In the contral group, IgG staining located in the blood vessels with littleleakage; while the IgG leakage was much more obvious in the diabetes group eight weeksafter the establishment of the model. Six weeks after intravitreal injection withSB203580, the leakage decreased in diabtes rats. The results of semi-quantitative analysisand fluorescence immunohistochemistry showed that compared with the results in diabetesrats 8 weeks after intravitreal injection (2.9 times much more than that in the controlgroup), the fluorescence expression of VEGF decreased in diabetes rats six weeks afterintravitreal injection (1.8 times much more than that in the control group). The apoptisisRGC number in rats 6 weeks after intravitreal injection of SB203580 was much less thanthat in rats without intravitreal injection (t=5. 731, P<0. 01). Conclusions SB203580can alleviate the disruption of BRB and apoptosis of RGC in early diabetes rats, whichsuggests that p38 MAPK pathways appear to be directly involved in the pathogenesis ofearly diabetic retinopathy. Key words: Diabetic retinopathy/Phisiopathology; P38 mitogen-activated proteinkinases/physiology; Blood-retinal barrier/physiology; Retinal ganglion cells/physiology; Diabetes mellitus, experimental