| Diabetic retinopathy (DR) is a vascular disease in the eyes triggered by diabetes, which is a leading cause of20to65years’old adult vision loss. As a microvascular disease, diabetic retinopathy results in the highest blindness rate in ophthalmology double-blind rate. The blindness rate triggered by diabetic retinopathy is25times than that in non-diabetic retinopathy. Therefore, it is high time to prevent and control diabetic retinopathy.Fufang Xueshuantong Capsule (FXT) is a common Chinese herbal composition in ophthalmology, which consists of Panax notoginseng, Salvia miltiorrhiza, Astragalus membranaceus, and Scrophularia ningpoensis. FXT could promote blood circulation to remove blood stasis, dilate the blood vessels, increase blood flux, improve blood circulation and microcirculation and tonify qi and yin, which has been used in clinical for nearly20years. A large number of clinical studies indicate that FXT could prevent fundus hemorrhage and microaneurysms in DR patients. In order to improve the quality of FXT to serve the masses of patients efficiently, steadily and safely, we transformed it and made new Fufang Xueshuantong formulas(Formula A and Formula B). The aim of the study is to investigate the effects and mechanisms of FXT and new formulas on diabetic retinopathy, in order to provide the research basis for optimizing the quality of FXT and offer new thought for the therapy of diabetic retinopathy.1. The effectiveness research of FXT on the early stages of diaberic retinopathy in ratsThe study aims at inducing diabetic rats and investigating the effects of FXT and new formulas on the change of common signs, blood glucose, hemorheology, blood vessels of retina in diabetic rats. Diabetes was induced in Sprague-Dawley rats by a single injection of60mg/kg streptozotocin. Treatment rats received FXT (1050mg/kg or525mg/kg), Formula A(36.6mg/kg or18.3mg/kg), Formula B(39.1mg/kg or19.5mg/kg) orally once daily for6months. A vehicle was administered orally to the control rats and untreated diabetic rats. Body weight and blood glucose were determined dynamically. Three indexes of hemorheology were assayed. Retinal morphometry were determined by trypsin digest preparations. The survival rate and change of lens were recorded, as well.Compared with control group, the survival rate of diabetic rats was72.9%, body weight increased very slowly, fasting blood glucose continued at a high level, the whole blood viscosity, plasma viscosity and erythrocyte aggregation index of STZ rats increased (p<0.05), the basement membrane of retinal vessel thickened, numbers of capillaries degenerated with occlusion, retinal venular caliber dilated, the number of pericytes reduced obviously. Compared with model group, the survival rate of FXT1050mg/kg, FXT525mg/kg and Formula B39.1mg/kg was lower slightly and the survival rate of Formula A36.6mg/kg, Formula A18.3mg/kg and Formula B19.5mg/kg elevated. In the trial, the body weight and blood glucose between all drugs treated groups and model group were not obvious. In hemorheology, FXT and Formula A were not dose-dependent.Compared with model rats, there was a decrease in the whole blood viscosity [60(1/s),1(1/s)], erythrocyte aggregation in FXT1050and525mg/kg group, but no change was found in the whole blood viscosity [200(1/s)] and plasma viscosity. There was a decrease in the whole blood viscosity [60(1/s),1(1/s)], erythrocyte aggregation index and plasma viscosity in Formula A36.6and18.3mg/kg group, but no change was found in the whole blood viscosity [200(1/s)]. Except for a decrease in the whole blood viscosity [200(1/s)], there was no change in other hemorheological indexs in Formula B19.5mg/kg group. However, Formula B39.1mg/kg could only reduce erythrocyte aggregation index in diabetic rats. Compared with model rats, there was a significant change in retinal blood vessels morphology in FXT1050mg/kg, FXT525mg/kg and Formula A36.6mg/kg group. The retinal vessel stain became shallow, retinal veins dilated unconspicuously, the number of pericytes increased, the number of acellular capillaries decreased. There was a weak improvement in retinal blood vessels form in other three groups relatively.2. The mechanism of FXT on the early stages of diaberic retimthy in ratsThe aim of this study is to investigate the mechanism of FXT and new formulas on the early stages of diaberic retinothy in rats. Diabetic model and drug-treatment were similar to part1. The activity of aldose reductase in retina was assayed by ultraviolet spectrophotometry. Expression of vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF) of retina were analysed by immunohistochemistry. Expression of occludin and intercellular adhesion molecule-1(ICAM-1) of retina was measured by Western blotting. Results Compared with control group, The expression of retinal VEGF raised (IOD/area0.66±0.28vs control0.25±0.03), the expression of retinal PEDF declined (IOD/area0.07±0.06vs control0.19±0.04), occludin protein decreased to70%, ICAM-1protein increased158%the activity of aldose reductase increased200%. Compared with model rats, there was a significant decrease in the activity of aldose reductase and the expression of VEGF (p<0.05) in all drug-treated groups. The expression of PEDF increased markedly in FXT (1050mg/kg,525mg/kg), Formula A (36.6mg/kg,18.3mg/kg). In addition, there were an increase in the expression of occludin and a decrease in the expression of ICAM-1in other drug-treated groups except in Formula B19.5mg/kg.In conclusion, FXT and its new formulas indicated a certain protective effect on diabetic retinopathy induced by STZ in rats, and the high-dose groups were better than the middle-dose groups. Compared with FXT, the curative effect of Formula A was similar to FXT, the curative effect of Formula B was weaker than FXT. Their effects may be related to regulate the activity of aldose reductase and the expression of VEGF, PEDF, occludin and ICAM-1. |
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